Italian scientists pioneering a new gene transfer treatment for the blood disorder β-thalassemia have successfully completed preclinical trials, claiming they can correct the lack of beta-globin (ß-globin) in patients' blood cells which causes the disease. The research, published in EMBO Molecular Medicine, reveals how gene therapy may represent a safe alternative to current cures that are limited to a minority of patients The disorder β-thalassemia, also known as Cooley's anemia, is caused when a patient cannot produce enough of the ß-globin component of haemoglobin, the protein used by red blood cells to carry oxygen around the body. The lack of ß-globin causes life threatening anemia, leading to severe damage of the body's major organs. The condition is most commonly found in Mediterranean, Middle Eastern and Asian populations.
"Currently treatments are limited to lifelong regular blood transfusions, and iron chelation to prevent fatal iron overload. The alternative is bone marrow transplantation, an option open to less than 25% of patients," said Dr Giuliana Ferrari from the San Raffaele Telethon Institute for Gene Therapy in Milan. "Our research has focused on gene therapy: by transplanting genetically corrected stem cells we can restore haemoglobin production and overcome the disorder."
Diseases of the blood are good targets for gene therapy because it is possible to harvest stem cells from the patient's bone marrow. The team developed a tool to deliver the correct gene for ß-globin into these harvested cells, a viral vector they called GLOBE.
The cells can then be genetically modified with GLOBE to restore hemoglobin production before being re-administered back into the patient via intravenous injections. The important focus of this work was not only to show that GLOBE can restore haemoglobin production in human cells, but that this genetic transfer-based approach does not impair the biological features of the cells and is not associated with any intrinsic risk for the human genome.
This research is not only crucial for developing a cure for one disease, but as Dr David Williams from the Harvard Medical School says, it may advance the entire discipline of gene therapy research
"This work represents the kind of translational studies that are required to move human investigations forward but are often difficult to fund and publish," said Williams. "Considering the inherent difficulties accompanying human research, studies like those reported in EMBO Molecular Medicine are extremely important for moving the field forward." As the Milan based team can now correct the defective production of beta-globin in patients' blood cells the next step will be to place the corrected cells back into the patient, a step which has already proven successful in mice.
Successful gene therapies are the results of very long studies and our research represents the most comprehensive pre-clinical analysis ever performed on cells derived from thalassemic patients" concluded Ferrari. "We believe this study paves the way forward for the clinical use of stem cells genetically corrected using the GLOBE vector."
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Aug 2, 2010
Experimental treatment for sickle cell disease enters Phase 3 clinical trials
An experimental treatment for sickle cell disease developed at the Los Angeles Biomedical Research Institute (LA BioMed) has entered Phase 3 clinical trials, David I. Meyer, PhD, LA BioMed president and CEO announced today.
Researchers throughout the U.S. have begun administering the sickle cell treatment developed by investigators led by Yutaka Niihara, MD, MPH, at LA BioMed and licensed to Emmaus Medical, Inc. The patented drug treatment involves the oral administration of L-glutamine, which is the most common amino acid in the body. This is one of a very few experimental treatments for sickle cell disease to reach the Phase 3 clinical trial stage.
Sickle cell disease is an inherited disorder that causes red blood cells to become oxidized, sticky and sickle shaped instead of smooth, pliable and round. Sickle cell disease leads to anemia, organ damage, chronic and acute pain and a host of other problems.
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"This is exciting news in the potential development of a novel new treatment for the millions of people who suffer from the painful effects of sickle cell disease," said Dr. Meyer. "We are proud of the dedication of Dr. Niihara and the team of researchers who first developed this treatment. They demonstrate the pioneering spirit that has kept LA BioMed at the forefront of translating discoveries into treatments that can transform lives."
Phase 3 clinical trials are large, randomized studies conducted at multiple sites to determine the safety and efficacy of a potential treatment. They are usually the last clinical trials conducted before the Food and Drug Administration gives its approval for a treatment to be made widely available to the patient population.
"As a physician I have seen firsthand the severe pain in patients with sickle cell disease, so I am very pleased we have reached this stage in our development of this potential treatment," said Dr. Niihara. "In the Phase 2 clinical trial, we observed an excellent safety profile and positive trends in decreasing the number of crises as well as reducing the frequency of hospitalizations in sickle cell disease patients. We look forward to the findings from the much larger group of research volunteers we will be seeking in the Phase 3 clinical trial."
In the Phase 3 clinical trial, researchers at 20 to 25 sites around the country will be seeking up to 225 research volunteers, age 5 years and older, with a diagnosis of sickle cell anemia or sickle beta O-thalassemia who have a history of at least two episodes of painful crisis during the past 12 months. The trial is a 53-week study requiring monthly visits to the research facility.
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Source: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)
Researchers throughout the U.S. have begun administering the sickle cell treatment developed by investigators led by Yutaka Niihara, MD, MPH, at LA BioMed and licensed to Emmaus Medical, Inc. The patented drug treatment involves the oral administration of L-glutamine, which is the most common amino acid in the body. This is one of a very few experimental treatments for sickle cell disease to reach the Phase 3 clinical trial stage.
Sickle cell disease is an inherited disorder that causes red blood cells to become oxidized, sticky and sickle shaped instead of smooth, pliable and round. Sickle cell disease leads to anemia, organ damage, chronic and acute pain and a host of other problems.
nullnullnull
"This is exciting news in the potential development of a novel new treatment for the millions of people who suffer from the painful effects of sickle cell disease," said Dr. Meyer. "We are proud of the dedication of Dr. Niihara and the team of researchers who first developed this treatment. They demonstrate the pioneering spirit that has kept LA BioMed at the forefront of translating discoveries into treatments that can transform lives."
Phase 3 clinical trials are large, randomized studies conducted at multiple sites to determine the safety and efficacy of a potential treatment. They are usually the last clinical trials conducted before the Food and Drug Administration gives its approval for a treatment to be made widely available to the patient population.
"As a physician I have seen firsthand the severe pain in patients with sickle cell disease, so I am very pleased we have reached this stage in our development of this potential treatment," said Dr. Niihara. "In the Phase 2 clinical trial, we observed an excellent safety profile and positive trends in decreasing the number of crises as well as reducing the frequency of hospitalizations in sickle cell disease patients. We look forward to the findings from the much larger group of research volunteers we will be seeking in the Phase 3 clinical trial."
In the Phase 3 clinical trial, researchers at 20 to 25 sites around the country will be seeking up to 225 research volunteers, age 5 years and older, with a diagnosis of sickle cell anemia or sickle beta O-thalassemia who have a history of at least two episodes of painful crisis during the past 12 months. The trial is a 53-week study requiring monthly visits to the research facility.
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Source: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)
Jul 26, 2010
Beta-Thalassemia: Gene Therapy Breakthrough
Italian scientists pioneering a new gene transfer treatment for the blood disorder β-thalassemia have successfully completed preclinical trials, claiming they can correct the lack of beta-globin (β-globin) in patients' blood cells which causes the disease. The research, published in EMBO Molecular Medicine, reveals how gene therapy may represent a safe alternative to current cures that are limited to a minority of patients.
The disorder β-thalassemia, also known as Cooley's anemia, is caused when a patient cannot produce enough of the β-globin component of haemoglobin, the protein used by red blood cells to carry oxygen around the body. The lack of β-globin causes life threatening anemia, leading to severe damage of the body's major organs. The condition is most commonly found in Mediterranean, Middle Eastern and Asian populations.
"Currently treatments are limited to lifelong regular blood transfusions, and iron chelation to prevent fatal iron overload. The alternative is bone marrow transplantation, an option open to less than 25% of patients," said Dr Giuliana Ferrari from the San Raffaele Telethon Institute for Gene Therapy in Milan. "Our research has focused on gene therapy: by transplanting genetically corrected stem cells we can restore haemoglobin production and overcome the disorder."
Diseases of the blood are good targets for gene therapy because it is possible to harvest stem cells from the patient's bone marrow. The team developed a tool to deliver the correct gene for ß-globin into these harvested cells, a viral vector they called GLOBE.
The cells can then be genetically modified with GLOBE to restore hemoglobin production before being re-administered back into the patient via intravenous injections. The important focus of this work was not only to show that GLOBE can restore haemoglobin production in human cells, but that this genetic transfer-based approach does not impair the biological features of the cells and is not associated with any intrinsic risk for the human genome.
This research is not only crucial for developing a cure for one disease, but as Dr David Williams from the Harvard Medical School says, it may advance the entire discipline of gene therapy research
"This work represents the kind of translational studies that are required to move human investigations forward but are often difficult to fund and publish," said Williams. "Considering the inherent difficulties accompanying human research, studies like those reported in EMBO Molecular Medicine are extremely important for moving the field forward." As the Milan based team can now correct the defective production of beta-globin in patients' blood cells the next step will be to place the corrected cells back into the patient, a step which has already proven successful in mice.
Successful gene therapies are the results of very long studies and our research represents the most comprehensive pre-clinical analysis ever performed on cells derived from thalassemic patients" concluded Ferrari. "We believe this study paves the way forward for the clinical use of stem cells genetically corrected using the GLOBE vector."
Source:
Ben Norman
Wiley-Blackwell
The disorder β-thalassemia, also known as Cooley's anemia, is caused when a patient cannot produce enough of the β-globin component of haemoglobin, the protein used by red blood cells to carry oxygen around the body. The lack of β-globin causes life threatening anemia, leading to severe damage of the body's major organs. The condition is most commonly found in Mediterranean, Middle Eastern and Asian populations.
"Currently treatments are limited to lifelong regular blood transfusions, and iron chelation to prevent fatal iron overload. The alternative is bone marrow transplantation, an option open to less than 25% of patients," said Dr Giuliana Ferrari from the San Raffaele Telethon Institute for Gene Therapy in Milan. "Our research has focused on gene therapy: by transplanting genetically corrected stem cells we can restore haemoglobin production and overcome the disorder."
Diseases of the blood are good targets for gene therapy because it is possible to harvest stem cells from the patient's bone marrow. The team developed a tool to deliver the correct gene for ß-globin into these harvested cells, a viral vector they called GLOBE.
The cells can then be genetically modified with GLOBE to restore hemoglobin production before being re-administered back into the patient via intravenous injections. The important focus of this work was not only to show that GLOBE can restore haemoglobin production in human cells, but that this genetic transfer-based approach does not impair the biological features of the cells and is not associated with any intrinsic risk for the human genome.
This research is not only crucial for developing a cure for one disease, but as Dr David Williams from the Harvard Medical School says, it may advance the entire discipline of gene therapy research
"This work represents the kind of translational studies that are required to move human investigations forward but are often difficult to fund and publish," said Williams. "Considering the inherent difficulties accompanying human research, studies like those reported in EMBO Molecular Medicine are extremely important for moving the field forward." As the Milan based team can now correct the defective production of beta-globin in patients' blood cells the next step will be to place the corrected cells back into the patient, a step which has already proven successful in mice.
Successful gene therapies are the results of very long studies and our research represents the most comprehensive pre-clinical analysis ever performed on cells derived from thalassemic patients" concluded Ferrari. "We believe this study paves the way forward for the clinical use of stem cells genetically corrected using the GLOBE vector."
Source:
Ben Norman
Wiley-Blackwell
Researchers discover genetic explanation for non-diabetic kidney disease in African-Americans
Variants in the APOL1 gene help explain high rates of renal disease in individuals of recent African ancestry; authors speculate that these variants originally evolved as a survival mechanism against parasitic disease in Africa
Kidney disease is a growing public health problem, with approximately half a million individuals in the United States requiring dialysis treatments to replace the function of their failed kidneys. The problem is particularly acute among African-Americans, whose rates of kidney disease are four times higher than those of European Americans.
As reported online this month by the journal Science, collaborating research groups found that patients with focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) harbored variants in the APOL1 gene that changed the ApoL1 protein sequence. These variants are commonly found in individuals of recent African ancestry.
Furthermore, in a twist of evolutionary medicine, the disease-causing variants may have protected Africans against a lethal parasite, explaining why these genetic variants are so common in the population today.
Researchers at Wake Forest University Baptist Medical Center contributed to and participated in this scientific team, led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and the Universite Libre de Bruxelles. Together, they discovered a genetic explanation - with evolutionary roots - for the higher incidence of non-diabetic kidney disease in African-Americans.
"We found that the APOL1 risk genes for renal disease occur in more than 30 percent of African-American chromosomes," explained co-senior author Martin Pollak, M.D., chief of nephrology at BIDMC and associate professor of medicine at Harvard Medical School. "In fact, the increased risk of kidney disease in individuals who inherited two copies of these variant forms of APOL1 is reported to be approximately 10-fold."
FSGS is a form of injury to the kidney's filtering system, which causes proteins to be lost into the urine and gradually reduces kidney function. ESKD, or end-stage kidney disease, is defined by kidney failure that has progressed to the point that the patient requires dialysis or kidney transplantation.
It has long been thought that high blood pressure is a common cause of end stage kidney disease in African-Americans," said study co-researcher Barry Freedman, M.D., John H. Felts III Professor and chief of the section on nephrology at WFUBMC. "However, the strong association between variants in the APOL1 gene and hypertension-attributed kidney disease suggested that this kidney disease truly resides in the spectrum of FSGS and is not due to hypertension as was initially believed."
More than 2,000 study participants from the southeastern United States were recruited to the study by WFUBMC.
Last year, Freedman led a team of WFUBMC researchers who found that genetic variation near the MYH9 gene on chromosome 22 was also associated with increased risk of hypertension-attributed kidney disease in African-Americans. However, because genome analyses had shown a strong signal of natural selection in the region containing both the MYH9 and APOL1 genes, the authors reasoned that the location of the disease-causing genetic variants was in a broader region. They also predicted that the frequency of these variants would be markedly different between European-Americans and Africans.
Using data from the 1000 Genomes Project DNA data bank, the authors identified candidate genetic variants and tested for their presence in DNA sample sets. They found that two APOL1 variants - dubbed G1 and G2 - were associated with an increased risk of both FSGS and hypertension-attributed ESKD in African-Americans.
"G1 and G2 both changed the coding sequence of APOL1," Pollak explained. "Further analyses revealed that these very same genetic variants [G1 and G2] conferred human immunity against the parasite responsible for sleeping sickness."
African sleeping sickness is caused by an African trypanosome parasite, which is transmitted by the tsetse fly. The disease, which produces severe nervous system disorders that can ultimately lead to brain damage, coma and death, is estimated to affect tens of thousands of people, but is not found outside of Africa.
The APOL1 protein circulates in the blood and helps defend against trypanosomes, a finding initially discovered by co-senior author Etienne Pays, Ph.D., of the Universite Libre de Bruxelles, in Belgium. In the current study, Pays' laboratory found that the plasma from patients harboring the G1 and G2 variants inactivated the trypanosomes that cause the deadliest forms of African Sleeping Sickness, as did the APOL1 protein with these same variants inserted.
"We were excited that our findings appeared to relate kidney disease in the United States with human evolution and parasite infection in Africa," Pollak said. "While there are many details that remain to be clarified in future studies, we do know that sickle-cell disease is a well-established precedent for this model, in which one copy of the mutation confers protection against a parasitic infection but two copies of the mutation can cause severe disease." Pollak explained that, when present in a single copy, certain hemoglobin mutations protect against malaria. But two copies cause sickle cell disease or thalassemia, severe red-blood cell diseases.
"It appears that we may have found a similar situation in APOL1," Pollack added. "Consequently, while these genetic variants protect against sleeping sickness, they also greatly increase a person's susceptibility to kidney disease. We hope that these new findings will not only lead us to a better understanding of the underlying mechanisms leading to kidney failure, but will also help us develop new ways to treat trypanosome infection and kidney disease."
Kidney disease is a growing public health problem, with approximately half a million individuals in the United States requiring dialysis treatments to replace the function of their failed kidneys. The problem is particularly acute among African-Americans, whose rates of kidney disease are four times higher than those of European Americans.
As reported online this month by the journal Science, collaborating research groups found that patients with focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) harbored variants in the APOL1 gene that changed the ApoL1 protein sequence. These variants are commonly found in individuals of recent African ancestry.
Furthermore, in a twist of evolutionary medicine, the disease-causing variants may have protected Africans against a lethal parasite, explaining why these genetic variants are so common in the population today.
Researchers at Wake Forest University Baptist Medical Center contributed to and participated in this scientific team, led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and the Universite Libre de Bruxelles. Together, they discovered a genetic explanation - with evolutionary roots - for the higher incidence of non-diabetic kidney disease in African-Americans.
"We found that the APOL1 risk genes for renal disease occur in more than 30 percent of African-American chromosomes," explained co-senior author Martin Pollak, M.D., chief of nephrology at BIDMC and associate professor of medicine at Harvard Medical School. "In fact, the increased risk of kidney disease in individuals who inherited two copies of these variant forms of APOL1 is reported to be approximately 10-fold."
FSGS is a form of injury to the kidney's filtering system, which causes proteins to be lost into the urine and gradually reduces kidney function. ESKD, or end-stage kidney disease, is defined by kidney failure that has progressed to the point that the patient requires dialysis or kidney transplantation.
It has long been thought that high blood pressure is a common cause of end stage kidney disease in African-Americans," said study co-researcher Barry Freedman, M.D., John H. Felts III Professor and chief of the section on nephrology at WFUBMC. "However, the strong association between variants in the APOL1 gene and hypertension-attributed kidney disease suggested that this kidney disease truly resides in the spectrum of FSGS and is not due to hypertension as was initially believed."
More than 2,000 study participants from the southeastern United States were recruited to the study by WFUBMC.
Last year, Freedman led a team of WFUBMC researchers who found that genetic variation near the MYH9 gene on chromosome 22 was also associated with increased risk of hypertension-attributed kidney disease in African-Americans. However, because genome analyses had shown a strong signal of natural selection in the region containing both the MYH9 and APOL1 genes, the authors reasoned that the location of the disease-causing genetic variants was in a broader region. They also predicted that the frequency of these variants would be markedly different between European-Americans and Africans.
Using data from the 1000 Genomes Project DNA data bank, the authors identified candidate genetic variants and tested for their presence in DNA sample sets. They found that two APOL1 variants - dubbed G1 and G2 - were associated with an increased risk of both FSGS and hypertension-attributed ESKD in African-Americans.
"G1 and G2 both changed the coding sequence of APOL1," Pollak explained. "Further analyses revealed that these very same genetic variants [G1 and G2] conferred human immunity against the parasite responsible for sleeping sickness."
African sleeping sickness is caused by an African trypanosome parasite, which is transmitted by the tsetse fly. The disease, which produces severe nervous system disorders that can ultimately lead to brain damage, coma and death, is estimated to affect tens of thousands of people, but is not found outside of Africa.
The APOL1 protein circulates in the blood and helps defend against trypanosomes, a finding initially discovered by co-senior author Etienne Pays, Ph.D., of the Universite Libre de Bruxelles, in Belgium. In the current study, Pays' laboratory found that the plasma from patients harboring the G1 and G2 variants inactivated the trypanosomes that cause the deadliest forms of African Sleeping Sickness, as did the APOL1 protein with these same variants inserted.
"We were excited that our findings appeared to relate kidney disease in the United States with human evolution and parasite infection in Africa," Pollak said. "While there are many details that remain to be clarified in future studies, we do know that sickle-cell disease is a well-established precedent for this model, in which one copy of the mutation confers protection against a parasitic infection but two copies of the mutation can cause severe disease." Pollak explained that, when present in a single copy, certain hemoglobin mutations protect against malaria. But two copies cause sickle cell disease or thalassemia, severe red-blood cell diseases.
"It appears that we may have found a similar situation in APOL1," Pollack added. "Consequently, while these genetic variants protect against sleeping sickness, they also greatly increase a person's susceptibility to kidney disease. We hope that these new findings will not only lead us to a better understanding of the underlying mechanisms leading to kidney failure, but will also help us develop new ways to treat trypanosome infection and kidney disease."
Jul 23, 2010
Pregnancy: Should I bank my baby's umbilical cord blood?
Your options
• Have your baby's cord blood collected and sent to a private cord blood bank or a public cord blood bank.
• Do not bank or donate your baby's cord blood.
Key points to remember•
Doctors do not recommend that you bank cord blood on the slight chance that your baby will need stem cells someday. If your baby were to need stem cells, he or she would probably need stem cells from someone else rather than his or her own stem cells.1
• Although privately banked cord blood is not likely to help your baby, it may help a sibling who has an illness that could be treated with a stem cell transplant. These include leukemia, sickle cell disease, Hodgkin's lymphoma, and thalassemia. Doctors recommend that you bank your baby's cord blood only if a family member already has one of these illnesses.
• You might consider donating the cord blood to a public bank instead. You probably won't be able to use the blood, but it could be used for research or for another child.
• Private cord blood banking is expensive. You will pay a starting fee of about $1,000 to $2,000, plus a storage fee of around $100 a year for as long as the blood is stored.
• If you want to save the cord blood, you must arrange for it ahead of time. It is not a decision you can make at the last minute.
• Collecting the cord blood does not cause pain.
What is umbilical cord blood?
Cord blood is the blood left in the umbilical cord after birth. It contains stem cells. These cells have the amazing ability to grow into many different kinds of cells, like bone marrow cells, blood cells, or brain cells. This can make them valuable for treating some diseases.
Diseases that can be treated with stem cell transplants include leukemia, Hodgkin’s disease, and some types of anemia. When healthy stem cells are transplanted into a child who is ill, those cells can grow new bone marrow cells to replace the ones destroyed by the disease or its treatment. Stem cells from the child's own cord blood often cannot be used, because they may have led to the disease in the first place.
Much research is being done to see if stem cells can be used to treat more problems. For now, though, treatment is limited to diseases that affect blood cells.
Cord blood kept in a private bank is usually used to treat disease in a brother or sister. Cord blood stem cells are rarely used to treat adults, who normally need more stem cells than cord blood has.
What is cord blood banking?
The umbilical cord is usually thrown away after birth. But the blood inside the cord can be saved, or banked, for possible later use. The blood is drawn from the umbilical cord after the cord has been clamped and cut. Cord blood banks freeze the cord blood for storage.
You may save your baby's cord blood in a private bank or donate it to a public bank. Private banks charge a fee to store cord blood for your family's use. If you donate the cord blood to a public bank, the cord blood can be used by anyone who needs it.
During your pregnancy, you may get ads or brochures from private cord blood banks. Some of them suggest that parents should save the cord blood in case the baby should one day need a stem cell transplant. Be wary of banks that urge cord blood banking for this reason. It is not known how likely a child is to need a transplant of his or her own cells, but experts say the chances are very small.1
Private cord blood banks have collected hundreds of thousands of cord blood samples. But the blood has been used in only a small number of transplants.2 Most transplants of cord blood stem cells use cord blood donated by others to public banks.
One reason why donations to public cord banks are so valuable is that stem cells from cord blood do not need to be as perfectly matched for a transplant as do stem cells from adult bone marrow. Stem cells from cord blood are not as mature, so the transplant patient's body is much less likely to reject them.
What are the risks of cord blood banking?
Collecting a baby’s cord blood is quick and does not cause pain. But it does have a small risk. The umbilical cord must not be clamped and cut too soon. Clamping as soon as possible increases how much blood is collected. But if it is done too quickly, it could cause the baby to have less blood. This could lead to anemia.
It is very unlikely that anyone in your family will ever need your baby's cord blood. The only people likely to use privately banked blood are those who already have a child with an illness that could be treated with cord blood from a baby brother or sister.1
It costs money to store your baby’s cord blood. Private banks charge about $1,000 to $2,000 to start. Then you must pay yearly storage fees for as long as the blood is stored. The storage fees cost $115 to $125 a year. Health plans usually do not cover these costs. Only you can decide if the cost makes sense for you and your family.
Doctors worry that the advertising done by private cord blood banks may make some parents feel guilty if they do not want or cannot pay to store their baby’s cord blood. Pregnancy and childbirth are emotional times, so learn all you can ahead of time.
What other things should you consider?
The American Academy of Pediatrics says storing cord blood in a private bank without a medical reason is not wise. This group of doctors recommends that you consider it only if a family member has a disease that could be treated with a stem cell transplant.3
Some private blood banks will waive their fees for families who need the stem cells right away.
If you bank or donate your baby's cord blood, it will be tested for genetic and infectious diseases. What you learn from a genetic test can affect your life and that of your family in many ways.
• Learning that your child is likely to develop a serious disease can be scary or depressing. This information may also affect your relationships with other family members.
• If your child tests positive for a gene that will cause a disease, you may decide to use treatment, if available, to prevent the disease or to make it less severe. Although many treatments work well, others may be unproven or may even be dangerous.
• Some people worry that gene test results will make it hard to get insurance.
Private banking: If you decide to bank your baby's cord blood, make sure that the blood bank you use is approved by a reputable regulatory agency, such as the American Association of Blood Banks. Look for a bank that has tested and stored many cord blood samples and whose samples have been used successfully in transplants. Ask for a copy of the bank's policies and procedures.
Public banking: You may decide that you would like to donate your baby’s cord blood. Donating makes the stem cells available to others. It does not cost anything. Unfortunately, it is not yet an option in many communities. Call the hospital where you plan to give birth to find out if you can donate cord blood there.
Why might your doctor recommend banking your baby's cord blood?
Your doctor might recommend privately banking your baby's umbilical cord blood if:
• You have another child who has a disease that could be treated with a stem cell transplant.
Compare your options
Bank cord blood Bank cord blood
What is usually involved?
• Long before birth, you arrange to bank your baby's cord blood.
• The blood is drawn from the umbilical cord after the cord has been clamped and cut.
• A cord blood bank freezes the cord blood for storage.
What are the benefits?•
Cord blood in a private bank could be used for a sibling who has an illness that can be treated with cord blood from a baby brother or sister.
• Giving the blood to a public cord bank could help research or some other child who needs it.
What are the risks and side effects?
• If the cord is clamped and cut too soon, your baby may become anemic.
• Private cord banking costs a lot. Banks charge $1,100 to $1,750 to start storage, then fees of more than $100 a year.
• Cord blood is tested for diseases. You could find out about a gene that may one day give your child a disease. This news could affect health insurance and job options.
Don't bank cord blood Don't bank cord blood
What is usually involved?
• The umbilical cord is thrown away after birth.
What are the benefits?
• You save money by not putting blood in a private cord bank.
• You avoid the small risk that the cord could be clamped and cut too soon. With less blood, the baby may become anemic.
What are the risks and side effects?
• Your child could later get an illness that could have been treated with a stem cell transplant. But experts say the chance that a child will need a transplant of his or her own cells is very small.1
nullnull
• Have your baby's cord blood collected and sent to a private cord blood bank or a public cord blood bank.
• Do not bank or donate your baby's cord blood.
Key points to remember•
Doctors do not recommend that you bank cord blood on the slight chance that your baby will need stem cells someday. If your baby were to need stem cells, he or she would probably need stem cells from someone else rather than his or her own stem cells.1
• Although privately banked cord blood is not likely to help your baby, it may help a sibling who has an illness that could be treated with a stem cell transplant. These include leukemia, sickle cell disease, Hodgkin's lymphoma, and thalassemia. Doctors recommend that you bank your baby's cord blood only if a family member already has one of these illnesses.
• You might consider donating the cord blood to a public bank instead. You probably won't be able to use the blood, but it could be used for research or for another child.
• Private cord blood banking is expensive. You will pay a starting fee of about $1,000 to $2,000, plus a storage fee of around $100 a year for as long as the blood is stored.
• If you want to save the cord blood, you must arrange for it ahead of time. It is not a decision you can make at the last minute.
• Collecting the cord blood does not cause pain.
What is umbilical cord blood?
Cord blood is the blood left in the umbilical cord after birth. It contains stem cells. These cells have the amazing ability to grow into many different kinds of cells, like bone marrow cells, blood cells, or brain cells. This can make them valuable for treating some diseases.
Diseases that can be treated with stem cell transplants include leukemia, Hodgkin’s disease, and some types of anemia. When healthy stem cells are transplanted into a child who is ill, those cells can grow new bone marrow cells to replace the ones destroyed by the disease or its treatment. Stem cells from the child's own cord blood often cannot be used, because they may have led to the disease in the first place.
Much research is being done to see if stem cells can be used to treat more problems. For now, though, treatment is limited to diseases that affect blood cells.
Cord blood kept in a private bank is usually used to treat disease in a brother or sister. Cord blood stem cells are rarely used to treat adults, who normally need more stem cells than cord blood has.
What is cord blood banking?
The umbilical cord is usually thrown away after birth. But the blood inside the cord can be saved, or banked, for possible later use. The blood is drawn from the umbilical cord after the cord has been clamped and cut. Cord blood banks freeze the cord blood for storage.
You may save your baby's cord blood in a private bank or donate it to a public bank. Private banks charge a fee to store cord blood for your family's use. If you donate the cord blood to a public bank, the cord blood can be used by anyone who needs it.
During your pregnancy, you may get ads or brochures from private cord blood banks. Some of them suggest that parents should save the cord blood in case the baby should one day need a stem cell transplant. Be wary of banks that urge cord blood banking for this reason. It is not known how likely a child is to need a transplant of his or her own cells, but experts say the chances are very small.1
Private cord blood banks have collected hundreds of thousands of cord blood samples. But the blood has been used in only a small number of transplants.2 Most transplants of cord blood stem cells use cord blood donated by others to public banks.
One reason why donations to public cord banks are so valuable is that stem cells from cord blood do not need to be as perfectly matched for a transplant as do stem cells from adult bone marrow. Stem cells from cord blood are not as mature, so the transplant patient's body is much less likely to reject them.
What are the risks of cord blood banking?
Collecting a baby’s cord blood is quick and does not cause pain. But it does have a small risk. The umbilical cord must not be clamped and cut too soon. Clamping as soon as possible increases how much blood is collected. But if it is done too quickly, it could cause the baby to have less blood. This could lead to anemia.
It is very unlikely that anyone in your family will ever need your baby's cord blood. The only people likely to use privately banked blood are those who already have a child with an illness that could be treated with cord blood from a baby brother or sister.1
It costs money to store your baby’s cord blood. Private banks charge about $1,000 to $2,000 to start. Then you must pay yearly storage fees for as long as the blood is stored. The storage fees cost $115 to $125 a year. Health plans usually do not cover these costs. Only you can decide if the cost makes sense for you and your family.
Doctors worry that the advertising done by private cord blood banks may make some parents feel guilty if they do not want or cannot pay to store their baby’s cord blood. Pregnancy and childbirth are emotional times, so learn all you can ahead of time.
What other things should you consider?
The American Academy of Pediatrics says storing cord blood in a private bank without a medical reason is not wise. This group of doctors recommends that you consider it only if a family member has a disease that could be treated with a stem cell transplant.3
Some private blood banks will waive their fees for families who need the stem cells right away.
If you bank or donate your baby's cord blood, it will be tested for genetic and infectious diseases. What you learn from a genetic test can affect your life and that of your family in many ways.
• Learning that your child is likely to develop a serious disease can be scary or depressing. This information may also affect your relationships with other family members.
• If your child tests positive for a gene that will cause a disease, you may decide to use treatment, if available, to prevent the disease or to make it less severe. Although many treatments work well, others may be unproven or may even be dangerous.
• Some people worry that gene test results will make it hard to get insurance.
Private banking: If you decide to bank your baby's cord blood, make sure that the blood bank you use is approved by a reputable regulatory agency, such as the American Association of Blood Banks. Look for a bank that has tested and stored many cord blood samples and whose samples have been used successfully in transplants. Ask for a copy of the bank's policies and procedures.
Public banking: You may decide that you would like to donate your baby’s cord blood. Donating makes the stem cells available to others. It does not cost anything. Unfortunately, it is not yet an option in many communities. Call the hospital where you plan to give birth to find out if you can donate cord blood there.
Why might your doctor recommend banking your baby's cord blood?
Your doctor might recommend privately banking your baby's umbilical cord blood if:
• You have another child who has a disease that could be treated with a stem cell transplant.
Compare your options
Bank cord blood Bank cord blood
What is usually involved?
• Long before birth, you arrange to bank your baby's cord blood.
• The blood is drawn from the umbilical cord after the cord has been clamped and cut.
• A cord blood bank freezes the cord blood for storage.
What are the benefits?•
Cord blood in a private bank could be used for a sibling who has an illness that can be treated with cord blood from a baby brother or sister.
• Giving the blood to a public cord bank could help research or some other child who needs it.
What are the risks and side effects?
• If the cord is clamped and cut too soon, your baby may become anemic.
• Private cord banking costs a lot. Banks charge $1,100 to $1,750 to start storage, then fees of more than $100 a year.
• Cord blood is tested for diseases. You could find out about a gene that may one day give your child a disease. This news could affect health insurance and job options.
Don't bank cord blood Don't bank cord blood
What is usually involved?
• The umbilical cord is thrown away after birth.
What are the benefits?
• You save money by not putting blood in a private cord bank.
• You avoid the small risk that the cord could be clamped and cut too soon. With less blood, the baby may become anemic.
What are the risks and side effects?
• Your child could later get an illness that could have been treated with a stem cell transplant. But experts say the chance that a child will need a transplant of his or her own cells is very small.1
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Alpha thalassemia X-linked mental retardation syndrome
What is alpha thalassemia X-linked mental retardation syndrome?
Alpha thalassemia X-linked mental retardation syndrome is an inherited disorder that affects many parts of the body. This condition occurs almost exclusively in males.
Males with alpha thalassemia X-linked mental retardation syndrome have intellectual disability and delayed development. Their speech is significantly delayed, and most never speak or sign more than a few words. Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with this disorder are never able to walk independently.
Almost everyone with alpha thalassemia X-linked mental retardation syndrome has distinctive facial features, including widely spaced eyes, a small nose with upturned nostrils, and low-set ears. The upper lip is shaped like an upside-down "V," and the lower lip tends to be prominent. These facial characteristics are most apparent in early childhood. Over time, the facial features become coarser, including a flatter face with a shortened nose.
Most affected individuals have mild signs of a blood disorder called alpha thalassemia. This disorder reduces the production of hemoglobin, which is the protein in red blood cells that carries oxygen to cells throughout the body. A reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Rarely, affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue.
Additional features of alpha thalassemia X-linked mental retardation syndrome include an unusually small head size (microcephaly), short stature, and skeletal abnormalities. Many affected individuals have problems with the digestive system, such as a backflow of stomach acids into the esophagus (gastroesophageal reflux) and chronic constipation. Genital abnormalities are also common; affected males may have undescended testes and the opening of the urethra on the underside of the penis (hypospadias). In more severe cases, the external genitalia do not look clearly male or female (ambiguous genitalia).
How common is alpha thalassemia X-linked mental retardation syndrome?Alpha thalassemia X-linked mental retardation syndrome appears to be a rare condition, although its exact prevalence is unknown. More than 200 affected individuals have been reported.
What genes are related to alpha thalassemia X-linked mental retardation syndrome?
Alpha thalassemia X-linked mental retardation syndrome results from mutations in the ATRX gene. This gene provides instructions for making a protein that plays an essential role in normal development. Although the exact function of the ATRX protein is unknown, studies suggest that it helps regulate the activity (expression) of other genes. Among these genes are HBA1 and HBA2, which are necessary for normal hemoglobin production.
Mutations in the ATRX gene change the structure of the ATRX protein, which likely prevents it from effectively regulating gene expression. Reduced activity of the HBA1 and HBA2 genes causes alpha thalassemia. Abnormal expression of other genes, which have not been identified, probably causes developmental delay, distinctive facial features, and the other signs and symptoms of alpha thalassemia X-linked mental retardation syndrome.
How do people inherit alpha thalassemia X-linked mental retardation syndrome?
This condition is inherited in an X-linked recessive pattern. The ATRX gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), one working copy of the ATRX gene can usually compensate for the mutated copy. Therefore, females who carry a single mutated ATRX gene almost never have signs of alpha thalassemia X-linked mental retardation.
A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
What other names do people use for alpha thalassemia X-linked mental retardation syndrome?• alpha-thalassemia/mental retardation syndrome, nondeletion type
• alpha thalassemia/mental retardation, X-linked
• alpha-thalassemia X-linked mental retardation syndrome
• ATRX syndrome
• ATR-X syndrome
• X-linked alpha-thalassemia/mental retardation syndrome
• XLMR-hypotonic face syndrome
Alpha thalassemia X-linked mental retardation syndrome is an inherited disorder that affects many parts of the body. This condition occurs almost exclusively in males.
Males with alpha thalassemia X-linked mental retardation syndrome have intellectual disability and delayed development. Their speech is significantly delayed, and most never speak or sign more than a few words. Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with this disorder are never able to walk independently.
Almost everyone with alpha thalassemia X-linked mental retardation syndrome has distinctive facial features, including widely spaced eyes, a small nose with upturned nostrils, and low-set ears. The upper lip is shaped like an upside-down "V," and the lower lip tends to be prominent. These facial characteristics are most apparent in early childhood. Over time, the facial features become coarser, including a flatter face with a shortened nose.
Most affected individuals have mild signs of a blood disorder called alpha thalassemia. This disorder reduces the production of hemoglobin, which is the protein in red blood cells that carries oxygen to cells throughout the body. A reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Rarely, affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue.
Additional features of alpha thalassemia X-linked mental retardation syndrome include an unusually small head size (microcephaly), short stature, and skeletal abnormalities. Many affected individuals have problems with the digestive system, such as a backflow of stomach acids into the esophagus (gastroesophageal reflux) and chronic constipation. Genital abnormalities are also common; affected males may have undescended testes and the opening of the urethra on the underside of the penis (hypospadias). In more severe cases, the external genitalia do not look clearly male or female (ambiguous genitalia).
How common is alpha thalassemia X-linked mental retardation syndrome?Alpha thalassemia X-linked mental retardation syndrome appears to be a rare condition, although its exact prevalence is unknown. More than 200 affected individuals have been reported.
What genes are related to alpha thalassemia X-linked mental retardation syndrome?
Alpha thalassemia X-linked mental retardation syndrome results from mutations in the ATRX gene. This gene provides instructions for making a protein that plays an essential role in normal development. Although the exact function of the ATRX protein is unknown, studies suggest that it helps regulate the activity (expression) of other genes. Among these genes are HBA1 and HBA2, which are necessary for normal hemoglobin production.
Mutations in the ATRX gene change the structure of the ATRX protein, which likely prevents it from effectively regulating gene expression. Reduced activity of the HBA1 and HBA2 genes causes alpha thalassemia. Abnormal expression of other genes, which have not been identified, probably causes developmental delay, distinctive facial features, and the other signs and symptoms of alpha thalassemia X-linked mental retardation syndrome.
How do people inherit alpha thalassemia X-linked mental retardation syndrome?
This condition is inherited in an X-linked recessive pattern. The ATRX gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), one working copy of the ATRX gene can usually compensate for the mutated copy. Therefore, females who carry a single mutated ATRX gene almost never have signs of alpha thalassemia X-linked mental retardation.
A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
What other names do people use for alpha thalassemia X-linked mental retardation syndrome?• alpha-thalassemia/mental retardation syndrome, nondeletion type
• alpha thalassemia/mental retardation, X-linked
• alpha-thalassemia X-linked mental retardation syndrome
• ATRX syndrome
• ATR-X syndrome
• X-linked alpha-thalassemia/mental retardation syndrome
• XLMR-hypotonic face syndrome
Jul 20, 2010
Immunization in Children and Adults who have Thalassemia
General Recommendations
Children who have thalassemia trait should be treated and immunized in a manner identical to all other children. The United States Center for Disease Control (CDC) has recently published an immunization schedule for 1998. This schedule represents the latest recommendations of this United States Government body. Their recommendations cover Hepatitis B vaccination, to be completed in the first year of life. Diphtheria, tetanus, and pertussis vaccination initially completed in the first 18 months of life with booster vaccination between 4 and 6 years and an adult tetanus booster between 14 and 16 years. Haemophilus influenzae conjugate vaccination completed by 15 months. Polio vaccination completed by 4 to 6 years, the first two vaccine doses optionally being the Salk IPV killed vaccine followed by the Sabin live oral vaccine. Measles, mumps and rubella vaccination completed by the age of 4 to 6 years. Varicella vaccine is recommended before the age of 18 months.
Hepatitis A VaccineChildren who have thalassemia intermedia or thalassemia major receive the above vaccines. In addition transfused children who test negative for Hepatitis A should be immunized against this virus whether or not they have been infected with Hepatitis C. Infection with Hepatitis A after infection Hepatitis C can lead to fulminant disease. It is not know whether late infection with this virus can cause worse hepatitis in individuals co-infected with other hepatitis viruses or with severe hemosiderosis.
Pneumococcal Vaccination
All children are immunized against Streptococcus pneumoniae with the 23-valent pneumococcal polysaccharide vaccine prior to splenectomy and boosters given every five years if their pneumococcal immunoglobin titers are negative. The conjugate pneumococcal vaccine is now available and should be considered for infants who have the possibility of early splenectomy; children who have Hemoglobin H Constant Spring might fall into this category. Children who have sickle thalassemia syndromes such as Sickle Beta Zero Thalassemia and Sickle Beta Plus Thalassemia should also receive either the conjugate vaccine as infants or the polysaccharide vaccine if they are over two years old. All children should receive boosters if they have negative titers to Streptococcus pneumoniae.
Influenza Vaccine
All children who have thalassemia intermedia or major should receive the influenza vaccine beginning at the age of six months (split vaccine with a booster the first season). Children who have other risk factors should also receive this vaccine.
HIV Infected Children
Children who are immune suppressed with HIV viral infection should not receive live virus vaccines: Measles, Mumps, Rubella; Oral Polio Vaccine; Varicella Vaccine. Nor should their siblings receive these vaccines without medical management to prevent infection of the immunosuppressed child.
Recommendations for children infected with the human immunodeficiency virus (HIV):
• All routine inactivated vaccines (IPV, Hib, Hepatitis B, and DTaP) are recommended for all children.
• Children who are six months or older receive the influenza vaccine (split dose with booster during the first season).
• Children who are two years old or older receive pneumococcal vaccine.
• The MMR vaccine is recommended only for children infected with HIV who are not severely immune compromised.
• Live virus vaccines are contraindicated in all children who are infected with HIV with the above exception.
Children Receiving Intravenous Gamma Globulin
Children who are receiving intravenous gamma globulin (IVIG) have the possibility that live virus vaccines will be inactivated or that they will not develop immunity.
Children After Bone Marrow Transplantation
Centers performing bone marrow transplantation each have their own preferred schedule for reimmunization of their patients. These schedules should be followed. After immunocompentence is documented and all other immunizations are complete these children should receive the influenza vaccination annually.
Other VaccinesNew vaccines are being developed and will be available periodically. The Rotavirus Vaccine has recently been released and is not specifically indicated for children who have thalassemia.
The meningococcal vaccine is available, but is not generally recommended in most references. It would be indicated for splenectomized children and adults. This vaccine is not thought to be optimal and is not routinely administered at this center.
Children who have thalassemia trait should be treated and immunized in a manner identical to all other children. The United States Center for Disease Control (CDC) has recently published an immunization schedule for 1998. This schedule represents the latest recommendations of this United States Government body. Their recommendations cover Hepatitis B vaccination, to be completed in the first year of life. Diphtheria, tetanus, and pertussis vaccination initially completed in the first 18 months of life with booster vaccination between 4 and 6 years and an adult tetanus booster between 14 and 16 years. Haemophilus influenzae conjugate vaccination completed by 15 months. Polio vaccination completed by 4 to 6 years, the first two vaccine doses optionally being the Salk IPV killed vaccine followed by the Sabin live oral vaccine. Measles, mumps and rubella vaccination completed by the age of 4 to 6 years. Varicella vaccine is recommended before the age of 18 months.
Hepatitis A VaccineChildren who have thalassemia intermedia or thalassemia major receive the above vaccines. In addition transfused children who test negative for Hepatitis A should be immunized against this virus whether or not they have been infected with Hepatitis C. Infection with Hepatitis A after infection Hepatitis C can lead to fulminant disease. It is not know whether late infection with this virus can cause worse hepatitis in individuals co-infected with other hepatitis viruses or with severe hemosiderosis.
Pneumococcal Vaccination
All children are immunized against Streptococcus pneumoniae with the 23-valent pneumococcal polysaccharide vaccine prior to splenectomy and boosters given every five years if their pneumococcal immunoglobin titers are negative. The conjugate pneumococcal vaccine is now available and should be considered for infants who have the possibility of early splenectomy; children who have Hemoglobin H Constant Spring might fall into this category. Children who have sickle thalassemia syndromes such as Sickle Beta Zero Thalassemia and Sickle Beta Plus Thalassemia should also receive either the conjugate vaccine as infants or the polysaccharide vaccine if they are over two years old. All children should receive boosters if they have negative titers to Streptococcus pneumoniae.
Influenza Vaccine
All children who have thalassemia intermedia or major should receive the influenza vaccine beginning at the age of six months (split vaccine with a booster the first season). Children who have other risk factors should also receive this vaccine.
HIV Infected Children
Children who are immune suppressed with HIV viral infection should not receive live virus vaccines: Measles, Mumps, Rubella; Oral Polio Vaccine; Varicella Vaccine. Nor should their siblings receive these vaccines without medical management to prevent infection of the immunosuppressed child.
Recommendations for children infected with the human immunodeficiency virus (HIV):
• All routine inactivated vaccines (IPV, Hib, Hepatitis B, and DTaP) are recommended for all children.
• Children who are six months or older receive the influenza vaccine (split dose with booster during the first season).
• Children who are two years old or older receive pneumococcal vaccine.
• The MMR vaccine is recommended only for children infected with HIV who are not severely immune compromised.
• Live virus vaccines are contraindicated in all children who are infected with HIV with the above exception.
Children Receiving Intravenous Gamma Globulin
Children who are receiving intravenous gamma globulin (IVIG) have the possibility that live virus vaccines will be inactivated or that they will not develop immunity.
Children After Bone Marrow Transplantation
Centers performing bone marrow transplantation each have their own preferred schedule for reimmunization of their patients. These schedules should be followed. After immunocompentence is documented and all other immunizations are complete these children should receive the influenza vaccination annually.
Other VaccinesNew vaccines are being developed and will be available periodically. The Rotavirus Vaccine has recently been released and is not specifically indicated for children who have thalassemia.
The meningococcal vaccine is available, but is not generally recommended in most references. It would be indicated for splenectomized children and adults. This vaccine is not thought to be optimal and is not routinely administered at this center.
Jul 19, 2010
Gene therapy represents safe alternative to current cures for blood disorder β-thalassemia
Italian scientists pioneering a new gene transfer treatment for the blood disorder β-thalassemia have successfully completed preclinical trials, claiming they can correct the lack of beta-globin (β-globin) in patients' blood cells which causes the disease. The research, published in EMBO Molecular Medicine, reveals how gene therapy may represent a safe alternative to current cures that are limited to a minority of patients.
The disorder β-thalassemia, also known as Cooley's anemia, is caused when a patient cannot produce enough of the β-globin component of haemoglobin, the protein used by red blood cells to carry oxygen around the body. The lack of β-globin causes life threatening anemia, leading to severe damage of the body's major organs. The condition is most commonly found in Mediterranean, Middle Eastern and Asian populations
"Currently treatments are limited to lifelong regular blood transfusions, and iron chelation to prevent fatal iron overload. The alternative is bone marrow transplantation, an option open to less than 25% of patients," said Dr Giuliana Ferrari from the San Raffaele Telethon Institute for Gene Therapy in Milan. "Our research has focused on gene therapy: by transplanting genetically corrected stem cells we can restore haemoglobin production and overcome the disorder."
Diseases of the blood are good targets for gene therapy because it is possible to harvest stem cells from the patient's bone marrow. The team developed a tool to deliver the correct gene for β-globin into these harvested cells, a viral vector they called GLOBE.
The cells can then be genetically modified with GLOBE to restore hemoglobin production before being re-administered back into the patient via intravenous injections. The important focus of this work was not only to show that GLOBE can restore haemoglobin production in human cells, but that this genetic transfer-based approach does not impair the biological features of the cells and is not associated with any intrinsic risk for the human genome.
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This research is not only crucial for developing a cure for one disease, but as Dr David Williams from the Harvard Medical School says, it may advance the entire discipline of gene therapy research.
"This work represents the kind of translational studies that are required to move human investigations forward but are often difficult to fund and publish," said Williams. "Considering the inherent difficulties accompanying human research, studies like those reported in EMBO Molecular Medicine are extremely important for moving the field forward." As the Milan based team can now correct the defective production of beta-globin in patients' blood cells the next step will be to place the corrected cells back into the patient, a step which has already proven successful in mice.
Successful gene therapies are the results of very long studies and our research represents the most comprehensive pre-clinical analysis ever performed on cells derived from thalassemic patients" concluded Ferrari. "We believe this study paves the way forward for the clinical use of stem cells genetically corrected using the GLOBE vector."
Source EMBO Molecular Medicine
The disorder β-thalassemia, also known as Cooley's anemia, is caused when a patient cannot produce enough of the β-globin component of haemoglobin, the protein used by red blood cells to carry oxygen around the body. The lack of β-globin causes life threatening anemia, leading to severe damage of the body's major organs. The condition is most commonly found in Mediterranean, Middle Eastern and Asian populations
"Currently treatments are limited to lifelong regular blood transfusions, and iron chelation to prevent fatal iron overload. The alternative is bone marrow transplantation, an option open to less than 25% of patients," said Dr Giuliana Ferrari from the San Raffaele Telethon Institute for Gene Therapy in Milan. "Our research has focused on gene therapy: by transplanting genetically corrected stem cells we can restore haemoglobin production and overcome the disorder."
Diseases of the blood are good targets for gene therapy because it is possible to harvest stem cells from the patient's bone marrow. The team developed a tool to deliver the correct gene for β-globin into these harvested cells, a viral vector they called GLOBE.
The cells can then be genetically modified with GLOBE to restore hemoglobin production before being re-administered back into the patient via intravenous injections. The important focus of this work was not only to show that GLOBE can restore haemoglobin production in human cells, but that this genetic transfer-based approach does not impair the biological features of the cells and is not associated with any intrinsic risk for the human genome.
null
This research is not only crucial for developing a cure for one disease, but as Dr David Williams from the Harvard Medical School says, it may advance the entire discipline of gene therapy research.
"This work represents the kind of translational studies that are required to move human investigations forward but are often difficult to fund and publish," said Williams. "Considering the inherent difficulties accompanying human research, studies like those reported in EMBO Molecular Medicine are extremely important for moving the field forward." As the Milan based team can now correct the defective production of beta-globin in patients' blood cells the next step will be to place the corrected cells back into the patient, a step which has already proven successful in mice.
Successful gene therapies are the results of very long studies and our research represents the most comprehensive pre-clinical analysis ever performed on cells derived from thalassemic patients" concluded Ferrari. "We believe this study paves the way forward for the clinical use of stem cells genetically corrected using the GLOBE vector."
Source EMBO Molecular Medicine
Indian children with AIDS from infected blood transfusions
by Nirmala Carvalho
Children with thalassemia need blood transfusions for treatment. In five years it has happened to thousands of children. Inadequate controls in Indian blood banks. For Pascoal Carvalho, immunologist and member of the Pontifical Council for Life, the solution exists and costs 16 euros: "We want the NAT, but the government must give subsidies to those who can’t afford it."
Jaipur (AsiaNews) - Three children who suffer from thalassemia in Jodhpur in Rajasthan this week contracted HIV after blood transfusions required to treat the disease. It is not the first time that such cases occur in India. According to statistics, over the past five years thousands of children have fallen ill with AIDS after blood transfusion from the state blood bank.
Marwar Thalassemic Society says that in the last six months eight children have contracted HIV and hepatitis C for 43 additional transfusions of infected blood. The three children are in care at the Ummed Hospital which treats children with thalassemia free of charge. Hospital managers said they had scrupulously followed the guidelines of the National AIDS Control Organization. Both hospitals blood banks are testing to verify that the donated blood is healthy, but often this is not enough.
"Tests of blood cells are not adequate," Pascoal Carvalho, immunologist and member of the Pontifical Council for life tells AsiaNews. "We need the Nucleic Acid Testing (NAT), but since it has a very high cost it is not always done".
Performing NAT on the blood cost 1000 rupees (16 Euros) and in most cases the cheaper Elisa test is carried out: "The Elisa test" continues the doctor, "often fails to identify the HIV virus, especially since detects it only after the virus has been circulating in the donor’s blood for three months".
India’s health system is well aware of the technologies needed to solve the problem, but does not invest: "The government must urgently upgrade its monitoring system in blood banks. The problem of infection is even more tragic because they are poor families who use government blood banks.
For Pascoal Carvalho, the only positive note is that better therapies are being introduced to treat thalassemia. But the doctor calls the government on its responsibilities: "The instruments for Nat cost 400 thousand rupees (6700 million) and 1000 rupees each test, but poor patients can not afford it. Only the government can require that Nat be used in all hospitals and blood banks and provide subsidies for those who must take the test. Only then will we avoid similar tragedies in India. "
Fr. Antonio Grugni, PIME missionary and doctor in Mumbai, told AsiaNews about the health situation in India: "The number of poor in India is enormous and they can only afford public health, where there are few doctors for a huge amount of patients. You can not say that the government does nothing: the cure for tuberculosis and leprosy are free, for example. It is not true that in India there is no money. There are but are often misused by individual states".
Children with thalassemia need blood transfusions for treatment. In five years it has happened to thousands of children. Inadequate controls in Indian blood banks. For Pascoal Carvalho, immunologist and member of the Pontifical Council for Life, the solution exists and costs 16 euros: "We want the NAT, but the government must give subsidies to those who can’t afford it."
Jaipur (AsiaNews) - Three children who suffer from thalassemia in Jodhpur in Rajasthan this week contracted HIV after blood transfusions required to treat the disease. It is not the first time that such cases occur in India. According to statistics, over the past five years thousands of children have fallen ill with AIDS after blood transfusion from the state blood bank.
Marwar Thalassemic Society says that in the last six months eight children have contracted HIV and hepatitis C for 43 additional transfusions of infected blood. The three children are in care at the Ummed Hospital which treats children with thalassemia free of charge. Hospital managers said they had scrupulously followed the guidelines of the National AIDS Control Organization. Both hospitals blood banks are testing to verify that the donated blood is healthy, but often this is not enough.
"Tests of blood cells are not adequate," Pascoal Carvalho, immunologist and member of the Pontifical Council for life tells AsiaNews. "We need the Nucleic Acid Testing (NAT), but since it has a very high cost it is not always done".
Performing NAT on the blood cost 1000 rupees (16 Euros) and in most cases the cheaper Elisa test is carried out: "The Elisa test" continues the doctor, "often fails to identify the HIV virus, especially since detects it only after the virus has been circulating in the donor’s blood for three months".
India’s health system is well aware of the technologies needed to solve the problem, but does not invest: "The government must urgently upgrade its monitoring system in blood banks. The problem of infection is even more tragic because they are poor families who use government blood banks.
For Pascoal Carvalho, the only positive note is that better therapies are being introduced to treat thalassemia. But the doctor calls the government on its responsibilities: "The instruments for Nat cost 400 thousand rupees (6700 million) and 1000 rupees each test, but poor patients can not afford it. Only the government can require that Nat be used in all hospitals and blood banks and provide subsidies for those who must take the test. Only then will we avoid similar tragedies in India. "
Fr. Antonio Grugni, PIME missionary and doctor in Mumbai, told AsiaNews about the health situation in India: "The number of poor in India is enormous and they can only afford public health, where there are few doctors for a huge amount of patients. You can not say that the government does nothing: the cure for tuberculosis and leprosy are free, for example. It is not true that in India there is no money. There are but are often misused by individual states".
Jun 14, 2010
Bone Marrow Stem Cells Reverse Sickle Cell Disease
By Drew Halley
A revolutionary new procedure for stem cell transplant is reversing the effects of severe adult sickle cell disease. For years, adults suffering from sickle cell anemia have relied on consistent blood transfusions and drug treatments to combat the disorder. Bone marrow transplants can reverse sickle cell, but have so far been restricted to children in the early stages of the disease. That is, until now.
Sickle cell anemia is a congenital blood disorder that affects all races, but is most common to persons with African ancestry, affecting about 72,000 in the US and millions worldwide. Red blood cells normally take the shape of a doughnut without its hole; in the blood of sickle cell patients, the cells assume an abnormal sickle shape. Sickle cells block small blood vessels and inhibit blood flow, which causes debilitating pain, damages organs and increases the risk of stroke. Many of the risks of sickle cell can be mediated through early diagnosis, dietary supplements, and drug treatment. But even with modern treatment, life expectancy for sickle cell patients is 42 in males, 48 in females. Some severe cases are resistant to existent therapies and can cut life even shorter.
Because red blood cells are produced in bone marrow, some high-risk children qualify for marrow transplants from a suitable sibling donor. Like all organ transplants, the procedure carries the danger of immune rejection, and so requires immunosuppressant drugs in addition to radiation therapy to kill diseased marrow. Transplants have been traditionally restricted to children, whose organs are comparably stronger than adults who suffer from the disease. Transplants are rare – there have been about 200 in the past few decades – and are attempted only in children whose disorders are life-threatening.
But a new procedure developed by the National Institute of Health (NIH) and Johns Hopkins University has successfully transplanted marrow to adults, reversing the disorder in 9 out of 10 patients. The new treatment uses significantly less radiation (about one fourth) to kill the patient’s existent marrow, combined with the immunosuppressant drug Sirolimus to reduce the likelihood of transplant rejection. By allowing more of the patient’s own marrow to remain, recovery from the transplant is faster and healthier (patients could previously spend months in germ-free isolation while their immune systems recovered). Thirty months after the transplant, the nine patients with successful transplants are healthy and show no side effects.
Many adults with sickle cell anemia take the drug hydroxyurea to treat the disorder. Hydroxyurea works by stimulating the body to produce a form of hemoglobin normally only found during development in the womb. The production of this hemoglobin type helps to balance the proportion of healthy vs. sickle cells in the blood, and reduces the damage done to lungs, kidneys, and liver (not to mention the risk of stroke). But hydroxyurea doesn’t work for all adult patients, making the prospect of adult marrow transplant a much-needed form of alternative therapy.
Kelly Halloway, the first half-match donation recipient at the National Institute of Health
So far, most adult patients who have received marrow transplants have had “full match” donors – siblings with a fully compatible genetic makeup. The chances of a sibling being fully matched are only 25%. But new procedures are expanding the pool of potential donors to “half match” donors, which includes parents and improves the likelihood of a compatible sibling to 75%. That means more sources of transplant marrow, and a better shot at a successful reversal of the disease.
Future research will aim to expand marrow transplants beyond sickle cell patients. Several other congenital blood diseases could conceivably be treated with marrow transplants, including such debilitating disorders as beta-thalassemia.Researchers are currently exploring the emerging possibilities of adult marrow transplants, and will doubtless yield more amazing treatments in coming years
A revolutionary new procedure for stem cell transplant is reversing the effects of severe adult sickle cell disease. For years, adults suffering from sickle cell anemia have relied on consistent blood transfusions and drug treatments to combat the disorder. Bone marrow transplants can reverse sickle cell, but have so far been restricted to children in the early stages of the disease. That is, until now.
Sickle cell anemia is a congenital blood disorder that affects all races, but is most common to persons with African ancestry, affecting about 72,000 in the US and millions worldwide. Red blood cells normally take the shape of a doughnut without its hole; in the blood of sickle cell patients, the cells assume an abnormal sickle shape. Sickle cells block small blood vessels and inhibit blood flow, which causes debilitating pain, damages organs and increases the risk of stroke. Many of the risks of sickle cell can be mediated through early diagnosis, dietary supplements, and drug treatment. But even with modern treatment, life expectancy for sickle cell patients is 42 in males, 48 in females. Some severe cases are resistant to existent therapies and can cut life even shorter.
Because red blood cells are produced in bone marrow, some high-risk children qualify for marrow transplants from a suitable sibling donor. Like all organ transplants, the procedure carries the danger of immune rejection, and so requires immunosuppressant drugs in addition to radiation therapy to kill diseased marrow. Transplants have been traditionally restricted to children, whose organs are comparably stronger than adults who suffer from the disease. Transplants are rare – there have been about 200 in the past few decades – and are attempted only in children whose disorders are life-threatening.
But a new procedure developed by the National Institute of Health (NIH) and Johns Hopkins University has successfully transplanted marrow to adults, reversing the disorder in 9 out of 10 patients. The new treatment uses significantly less radiation (about one fourth) to kill the patient’s existent marrow, combined with the immunosuppressant drug Sirolimus to reduce the likelihood of transplant rejection. By allowing more of the patient’s own marrow to remain, recovery from the transplant is faster and healthier (patients could previously spend months in germ-free isolation while their immune systems recovered). Thirty months after the transplant, the nine patients with successful transplants are healthy and show no side effects.
Many adults with sickle cell anemia take the drug hydroxyurea to treat the disorder. Hydroxyurea works by stimulating the body to produce a form of hemoglobin normally only found during development in the womb. The production of this hemoglobin type helps to balance the proportion of healthy vs. sickle cells in the blood, and reduces the damage done to lungs, kidneys, and liver (not to mention the risk of stroke). But hydroxyurea doesn’t work for all adult patients, making the prospect of adult marrow transplant a much-needed form of alternative therapy.
Kelly Halloway, the first half-match donation recipient at the National Institute of Health
So far, most adult patients who have received marrow transplants have had “full match” donors – siblings with a fully compatible genetic makeup. The chances of a sibling being fully matched are only 25%. But new procedures are expanding the pool of potential donors to “half match” donors, which includes parents and improves the likelihood of a compatible sibling to 75%. That means more sources of transplant marrow, and a better shot at a successful reversal of the disease.
Future research will aim to expand marrow transplants beyond sickle cell patients. Several other congenital blood diseases could conceivably be treated with marrow transplants, including such debilitating disorders as beta-thalassemia.Researchers are currently exploring the emerging possibilities of adult marrow transplants, and will doubtless yield more amazing treatments in coming years
Jun 11, 2010
Indians at Risk for Rare Blood Disorder Thalassemia
By LISA TSERING
indiawest.com
Indian Americans are at greater risk of contracting thalassemia than many other ethnic groups, according to a study by the Children’s Hospital and Research Center Oakland in Oakland, Calif. To coincide with International Thalassemia Day May 8, the hospital is urging the community to get tested — and to seriously consider banking their infants’ cord blood.
The rare and hereditary blood disorder can result in severe anemia. Children with thalassemia often require frequent blood transfusions and lifelong medical treatment.
Gargi Pahuja, a health care law attorney in New York, was diagnosed with thalassemia when she was 12 months old. “My parents were from India and they hadn’t heard of it,” Pahuja told India-West in a phone interview. “They were shocked to find that they carried the trait.”
Since thalassemia is so rare, some doctors are likely to confuse its symptoms, which include yellow skin, with jaundice. But thalassemia is a much more serious disease.
Thalassemia (also known as Mediterranean anemia) is an inherited blood disorder characterized by less hemoglobin and fewer red blood cells in the body than normal. Since hemoglobin allows red blood cells to carry oxygen, a deficiency leads to anemia, marked by fatigue, pale appearance, shortness of breath and weakness.
Pahuja is 35 years old, and continues to get blood transfusions every two weeks.
“The fact that I’m 35 is an important milestone,” she told India-West. “My parents were told that I would die by the age of 15 … my generation is the first to live into their 30s, 40s and 50s.”
The cause of thalassemia is defects in the genes that make hemoglobin. The only way to contract thalassemia is to inherit one or more defective hemoglobin genes from your parents.
Infants in California are required to receive a test for thalassemia, but California is the only state to require the test, said Pahuja.
Bone marrow transplant is the established treatment to cure thalassemia. Umbilical cord blood stem cells donated by a sibling have been proven to cure 91 percent of cases, according to a 2007 Children’s Hospital study of 40 children.
A Mayo Clinic statement said that most children with moderate to severe thalassemia show signs within the first two years of life. Prenatal testing is also available, at 11 weeks (chorionic villus sampling), 16 weeks (amniocentesis), and 18 weeks (fetal blood sampling).
“People need to be tested so that they can make informed decisions regarding family planning,” said Pahuja.
The Children’s Hospital study showed that in the United States, around two million people are carriers and that around 1,000 people have the full-blown disease. The hospital has one of the largest thalassemia centers on the West Coast, and currently treats around 300 patients.
In the U.S., there are more than 5,000 thalassemia cases, and those numbers are expected
to rise as the trait carrier population increases, said the study; in Alameda County alone, the Asian Indian population is more than 47,000 and has increased by 209 percent in the last decade, according to statistics provided by the Asian American Pacific Islander Health Forum.
According to Pahuja — who says she has devoted her professional and personal life to increasing awareness of thalassemia — people from North India are especially at risk. “If you are Punjabi, or Gujarati, or Sindhi, you need to get tested,” she told India-West. Individuals who are past child-bearing age need not get tested, she added.
In India, as many as one in eight people are believed to be carriers of the thalassemia gene, and in India, it is expected that 1 million people will have the disease in the next 40 years. Babies born there are 80-90 percent likely to die of the disease, said the Children’s Hospital spokesperson. But increasing awareness of the disease there has opened up a market for blood cord banking; a recent Mumbai Mirror article states that there are now three private stem cell banks — one run by Reliance in Mumbai; the CryoCell stem bank in New Delhi; and Life Cell, run in collaboration with Cryo-Cell International, U.S.A., in Chennai.
In India, it costs around Rs. 70,000 ($1,575) to preserve a newborn’s cord blood for 20 years. Here in the United States, the average cost is around $2,000.
indiawest.com
Indian Americans are at greater risk of contracting thalassemia than many other ethnic groups, according to a study by the Children’s Hospital and Research Center Oakland in Oakland, Calif. To coincide with International Thalassemia Day May 8, the hospital is urging the community to get tested — and to seriously consider banking their infants’ cord blood.
The rare and hereditary blood disorder can result in severe anemia. Children with thalassemia often require frequent blood transfusions and lifelong medical treatment.
Gargi Pahuja, a health care law attorney in New York, was diagnosed with thalassemia when she was 12 months old. “My parents were from India and they hadn’t heard of it,” Pahuja told India-West in a phone interview. “They were shocked to find that they carried the trait.”
Since thalassemia is so rare, some doctors are likely to confuse its symptoms, which include yellow skin, with jaundice. But thalassemia is a much more serious disease.
Thalassemia (also known as Mediterranean anemia) is an inherited blood disorder characterized by less hemoglobin and fewer red blood cells in the body than normal. Since hemoglobin allows red blood cells to carry oxygen, a deficiency leads to anemia, marked by fatigue, pale appearance, shortness of breath and weakness.
Pahuja is 35 years old, and continues to get blood transfusions every two weeks.
“The fact that I’m 35 is an important milestone,” she told India-West. “My parents were told that I would die by the age of 15 … my generation is the first to live into their 30s, 40s and 50s.”
The cause of thalassemia is defects in the genes that make hemoglobin. The only way to contract thalassemia is to inherit one or more defective hemoglobin genes from your parents.
Infants in California are required to receive a test for thalassemia, but California is the only state to require the test, said Pahuja.
Bone marrow transplant is the established treatment to cure thalassemia. Umbilical cord blood stem cells donated by a sibling have been proven to cure 91 percent of cases, according to a 2007 Children’s Hospital study of 40 children.
A Mayo Clinic statement said that most children with moderate to severe thalassemia show signs within the first two years of life. Prenatal testing is also available, at 11 weeks (chorionic villus sampling), 16 weeks (amniocentesis), and 18 weeks (fetal blood sampling).
“People need to be tested so that they can make informed decisions regarding family planning,” said Pahuja.
The Children’s Hospital study showed that in the United States, around two million people are carriers and that around 1,000 people have the full-blown disease. The hospital has one of the largest thalassemia centers on the West Coast, and currently treats around 300 patients.
In the U.S., there are more than 5,000 thalassemia cases, and those numbers are expected
to rise as the trait carrier population increases, said the study; in Alameda County alone, the Asian Indian population is more than 47,000 and has increased by 209 percent in the last decade, according to statistics provided by the Asian American Pacific Islander Health Forum.
According to Pahuja — who says she has devoted her professional and personal life to increasing awareness of thalassemia — people from North India are especially at risk. “If you are Punjabi, or Gujarati, or Sindhi, you need to get tested,” she told India-West. Individuals who are past child-bearing age need not get tested, she added.
In India, as many as one in eight people are believed to be carriers of the thalassemia gene, and in India, it is expected that 1 million people will have the disease in the next 40 years. Babies born there are 80-90 percent likely to die of the disease, said the Children’s Hospital spokesperson. But increasing awareness of the disease there has opened up a market for blood cord banking; a recent Mumbai Mirror article states that there are now three private stem cell banks — one run by Reliance in Mumbai; the CryoCell stem bank in New Delhi; and Life Cell, run in collaboration with Cryo-Cell International, U.S.A., in Chennai.
In India, it costs around Rs. 70,000 ($1,575) to preserve a newborn’s cord blood for 20 years. Here in the United States, the average cost is around $2,000.
Signs of Anemia in an Infant
By:Ashley Waters Gordon
Overview
Anemia is a common blood disorder in infants, affecting normal growth and development. The most common type in babies under two years of age is iron-deficiency anemia. With iron-deficiency anemia, the infant either does not get enough iron or cannot absorb iron. Lack of iron lowers the number of healthy red blood cells. These contain hemoglobin, which carries oxygen to organs and tissues. A growing baby needs this oxygen for organs to develop properly. Signs of infant anemia can be hard to see until the case is more severe, so have your baby tested at routine doctor's appointments. Call your infant's pediatrician right away if you notice any of the below symptoms.
Paleness of Skin, Lips and Nail Beds
Look for paleness in your baby's skin, lips or nail beds. Paleness tells you that not enough red blood cells and oxygen are circulating in your baby's blood. Some babies can even take on a gray or blue tone in very serious cases. You may not be able to notice paleness in infants until they have significant anemia, typically hemoglobin levels greater than 7 grams per deciliter (g/dL). Schedule an appointment for your baby to see his pediatrician if you notice paleness.
Growth or Developmental Delays
Pay attention to any delays in your baby's growth and development. These delays may be signs of anemia. Delayed growth and development can happen when the baby's organs, like the heart or the brain, do not getting enough oxygen to grow properly. Talk with your baby's pediatrician at his next appointment if you feel that your baby is not growing at the same rate or is not reaching normal developmental milestones.
Jaundice
Anemic babies can develop a condition called jaundice. You will be able to see jaundice when the infant's skin or whites of the eyes turn a yellow color. The buildup of a substance called bilirubin causes this yellowing. This happens when the baby's body breaks down too many old red blood cells, making a large amount of bilirubin. The baby's liver can filter out a normal amount of bilirubin each day. When there is a high number of red blood cells broken down and more bilirubin than the liver can handle, your infant's skin begins to turn yellow. Call your baby's pediatrician immediately if you notice any yellowing of the skin so that she can begin treating your baby's jaundice and anemia.
Rapid Heartbeat or New Heart Murmur
Pay attention to heart changes. When not enough oxygen is getting to your baby's tissues and organs, her body may compensate by raising her heart rate. The heart tries to pump more blood and oxygen to tissues throughout her body. Stress on the heart can cause a murmur. Ask the pediatrician if anemia could be causing your baby's increased heart rate or new murmur. If anemia could be the cause, have your infant's blood tested for anemia.
Decreased Appetite
Babies with anemia become tired easily and may be too weak to properly suck. If you notice your baby has a decreased appetite, begin taking notes of how often and for how long your baby nurses. Or, if your baby drinks formula, make note of the volume of formula your baby drinks at each feeding. Share this information with your pediatrician.
Excessive Sleeping or Fatigue
If your baby sleeps an excessive amount, call your pediatrician. This can be a sign of anemia. Because he does not have enough oxygen in his blood, an anemic baby may be too weak to play or remain awake for normal periods of time. Keep a journal of how long your baby sleeps in a 24-hour period. When your baby is awake, make notes on how active he stays. Show the pediatrician your notes to help diagnose and treat any possible anemia.
Irritability
Does your baby seem unusually cranky when she is awake? If she has anemia, your infant may be over-tired, or hungry but too weak to eat. This can make a baby become more irritable than normal. Ask your doctor if your baby's irritability maybe a sign of underlying anemia.
Overview
Anemia is a common blood disorder in infants, affecting normal growth and development. The most common type in babies under two years of age is iron-deficiency anemia. With iron-deficiency anemia, the infant either does not get enough iron or cannot absorb iron. Lack of iron lowers the number of healthy red blood cells. These contain hemoglobin, which carries oxygen to organs and tissues. A growing baby needs this oxygen for organs to develop properly. Signs of infant anemia can be hard to see until the case is more severe, so have your baby tested at routine doctor's appointments. Call your infant's pediatrician right away if you notice any of the below symptoms.
Paleness of Skin, Lips and Nail Beds
Look for paleness in your baby's skin, lips or nail beds. Paleness tells you that not enough red blood cells and oxygen are circulating in your baby's blood. Some babies can even take on a gray or blue tone in very serious cases. You may not be able to notice paleness in infants until they have significant anemia, typically hemoglobin levels greater than 7 grams per deciliter (g/dL). Schedule an appointment for your baby to see his pediatrician if you notice paleness.
Growth or Developmental Delays
Pay attention to any delays in your baby's growth and development. These delays may be signs of anemia. Delayed growth and development can happen when the baby's organs, like the heart or the brain, do not getting enough oxygen to grow properly. Talk with your baby's pediatrician at his next appointment if you feel that your baby is not growing at the same rate or is not reaching normal developmental milestones.
Jaundice
Anemic babies can develop a condition called jaundice. You will be able to see jaundice when the infant's skin or whites of the eyes turn a yellow color. The buildup of a substance called bilirubin causes this yellowing. This happens when the baby's body breaks down too many old red blood cells, making a large amount of bilirubin. The baby's liver can filter out a normal amount of bilirubin each day. When there is a high number of red blood cells broken down and more bilirubin than the liver can handle, your infant's skin begins to turn yellow. Call your baby's pediatrician immediately if you notice any yellowing of the skin so that she can begin treating your baby's jaundice and anemia.
Rapid Heartbeat or New Heart Murmur
Pay attention to heart changes. When not enough oxygen is getting to your baby's tissues and organs, her body may compensate by raising her heart rate. The heart tries to pump more blood and oxygen to tissues throughout her body. Stress on the heart can cause a murmur. Ask the pediatrician if anemia could be causing your baby's increased heart rate or new murmur. If anemia could be the cause, have your infant's blood tested for anemia.
Decreased Appetite
Babies with anemia become tired easily and may be too weak to properly suck. If you notice your baby has a decreased appetite, begin taking notes of how often and for how long your baby nurses. Or, if your baby drinks formula, make note of the volume of formula your baby drinks at each feeding. Share this information with your pediatrician.
Excessive Sleeping or Fatigue
If your baby sleeps an excessive amount, call your pediatrician. This can be a sign of anemia. Because he does not have enough oxygen in his blood, an anemic baby may be too weak to play or remain awake for normal periods of time. Keep a journal of how long your baby sleeps in a 24-hour period. When your baby is awake, make notes on how active he stays. Show the pediatrician your notes to help diagnose and treat any possible anemia.
Irritability
Does your baby seem unusually cranky when she is awake? If she has anemia, your infant may be over-tired, or hungry but too weak to eat. This can make a baby become more irritable than normal. Ask your doctor if your baby's irritability maybe a sign of underlying anemia.
May 24, 2010
Study Looks at Pregnancy in Thalassemia
A recent study published in Haematologica (Vol. 95, Issue 3) examined pregnancy in women with thalassemia.
Entitled "Pregnancy and Beta-thalassemia: an Italian multicenter experience," the paper examined 58 pregnancies among 47 women with thalassemia major and 17 pregnancies in women with thalassemia intermedia at four centers in Italy. The study reports that conception was spontaneous in all of those with thalassemia intermedia; among those with thalassemia major, gonadotrophin-induced ovulation was required in 33 of the women.
According to the study, 91% of the pregnancies among alassemia major patients resulted in live births (45 single births, 5 sets of twins, one set of triplets). The authors also report that no secondary complications of iron overload developed or worsened during pregnancy. There was a higher prevalence of pre-term births (32.8%), but the authors state that this was primarily related to multiple pregnancies and precautionary measures. Women with thalassemia intermedia who had never been transfused or who had only minimal transfusion prior to pregnancy were found to be at risk of severe alloimmune anemia if transfusions were required during pregnancy. (Decreased hemoglobin levels necessitated transfusion in 11 of the 17 thalassemia intermedia pregnancies.) Of the 17 pregnancies in thalassemia intermedia known to the researchers, 15 resulted in live births.
The authors also state that "cardiac function was not impaired during pregnancy." One patient did experience worsening of T2* scores, but the authors suggest that this was due to the timing of the second MRI reading; as it was taken one month after delivery, the patient was still off chelation. The authors also stated that "it is strongly recommended that thalassemic women wishing to become pregnant undergo a complete evaluation of organ iron overload, including MRI T2* and SQUID, prior to pregnancy." (In the United States, Ferriscan/R2 readings are often used for liver iron rather than those provided by SQUID, together with T2* cardiac assessment.)
The study concludes that "provided a multidisciplinary team is available, pregnancy is possible, safe and usually has a favorable outcome in patients with thalassemia." The authors are state the need for larger and more detailed studies, especially in thalassemia intermedia.
Download CAF's "Fertility and Pregnancy in Thalassemia" pamphlet by clicking here
Entitled "Pregnancy and Beta-thalassemia: an Italian multicenter experience," the paper examined 58 pregnancies among 47 women with thalassemia major and 17 pregnancies in women with thalassemia intermedia at four centers in Italy. The study reports that conception was spontaneous in all of those with thalassemia intermedia; among those with thalassemia major, gonadotrophin-induced ovulation was required in 33 of the women.
According to the study, 91% of the pregnancies among alassemia major patients resulted in live births (45 single births, 5 sets of twins, one set of triplets). The authors also report that no secondary complications of iron overload developed or worsened during pregnancy. There was a higher prevalence of pre-term births (32.8%), but the authors state that this was primarily related to multiple pregnancies and precautionary measures. Women with thalassemia intermedia who had never been transfused or who had only minimal transfusion prior to pregnancy were found to be at risk of severe alloimmune anemia if transfusions were required during pregnancy. (Decreased hemoglobin levels necessitated transfusion in 11 of the 17 thalassemia intermedia pregnancies.) Of the 17 pregnancies in thalassemia intermedia known to the researchers, 15 resulted in live births.
The authors also state that "cardiac function was not impaired during pregnancy." One patient did experience worsening of T2* scores, but the authors suggest that this was due to the timing of the second MRI reading; as it was taken one month after delivery, the patient was still off chelation. The authors also stated that "it is strongly recommended that thalassemic women wishing to become pregnant undergo a complete evaluation of organ iron overload, including MRI T2* and SQUID, prior to pregnancy." (In the United States, Ferriscan/R2 readings are often used for liver iron rather than those provided by SQUID, together with T2* cardiac assessment.)
The study concludes that "provided a multidisciplinary team is available, pregnancy is possible, safe and usually has a favorable outcome in patients with thalassemia." The authors are state the need for larger and more detailed studies, especially in thalassemia intermedia.
Download CAF's "Fertility and Pregnancy in Thalassemia" pamphlet by clicking here
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