Find information on thousands of medical conditions and prescription drugs.

Anemia, Diamond-Blackfan

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy. DBA patients have low red blood cell counts (anemia). The rest of their blood cells (the platelets and the white blood cells) are normal. A variety of other congenital abnormalities may also occur. more...

Aagenaes syndrome
Aarskog Ose Pande syndrome
Aarskog syndrome
Aase Smith syndrome
Aase syndrome
ABCD syndrome
Abdallat Davis Farrage...
Abdominal aortic aneurysm
Abdominal cystic...
Abdominal defects
Absence of Gluteal muscle
Accessory pancreas
Achard syndrome
Achard-Thiers syndrome
Achondrogenesis type 1A
Achondrogenesis type 1B
Achondroplastic dwarfism
Acid maltase deficiency
Ackerman syndrome
Acne rosacea
Acoustic neuroma
Acquired ichthyosis
Acquired syphilis
Acrofacial dysostosis,...
Activated protein C...
Acute febrile...
Acute intermittent porphyria
Acute lymphoblastic leukemia
Acute lymphocytic leukemia
Acute mountain sickness
Acute myelocytic leukemia
Acute myelogenous leukemia
Acute necrotizing...
Acute promyelocytic leukemia
Acute renal failure
Acute respiratory...
Acute tubular necrosis
Adams Nance syndrome
Adams-Oliver syndrome
Addison's disease
Adducted thumb syndrome...
Adenoid cystic carcinoma
Adenosine deaminase...
Adenosine monophosphate...
Adie syndrome
Adrenal incidentaloma
Adrenal insufficiency
Adrenocortical carcinoma
Adrenogenital syndrome
Aicardi syndrome
AIDS Dementia Complex
Albright's hereditary...
Alcohol fetopathy
Alcoholic hepatitis
Alcoholic liver cirrhosis
Alexander disease
Alien hand syndrome
Alopecia areata
Alopecia totalis
Alopecia universalis
Alpers disease
Alpha 1-antitrypsin...
Alport syndrome
Alternating hemiplegia
Alzheimer's disease
Ambras syndrome
Amelogenesis imperfecta
American trypanosomiasis
Amyotrophic lateral...
Androgen insensitivity...
Anemia, Diamond-Blackfan
Anemia, Pernicious
Anemia, Sideroblastic
Aneurysm of sinus of...
Angelman syndrome
Ankylosing spondylitis
Annular pancreas
Anorexia nervosa
Anthrax disease
Antiphospholipid syndrome
Antisocial personality...
Antithrombin deficiency,...
Anton's syndrome
Aortic aneurysm
Aortic coarctation
Aortic dissection
Aortic valve stenosis
Apert syndrome
Aphthous stomatitis
Aplastic anemia
Argininosuccinic aciduria
Arnold-Chiari malformation
Arrhythmogenic right...
Arteriovenous malformation
Arthritis, Juvenile
Arthrogryposis multiplex...
Aseptic meningitis
Asherman's syndrome
Asphyxia neonatorum
Ataxia telangiectasia
Atelosteogenesis, type II
Atopic Dermatitis
Atrial septal defect
Atrioventricular septal...
Attention Deficit...
Autoimmune hepatitis
Autonomic dysfunction
Familial Alzheimer disease

Clinical Features

Diamond-Blackfan anemia is characterized by anemia (low red blood cell counts) with decreased erythroid progenitors in the bone marrow. This usually develops during the neonatal period. About 47% of affected individuals also have a variety of congenital abnormalities, including craniofacial malformations, thumb or upper limb abnormalities, cardiac defects, urogenital malformations, and cleft palate. Low birth weight and generalized growth retardation are sometimes observed. DBA patients have a modest risk of developing leukemia and other malignancies.


A diagnosis of DBA is made on the basis of anemia, low reticulocyte (immature red blood cells) counts, and diminished erythroid precursors in bone marrow. Features that support a diagnosis of DBA include the presence of congenital abnormalities, macrocytosis, elevated fetal hemoglobin, and elevated adenosine deaminase levels in red blood cells. Most patients are diagnosed in the first two years of life. However, some mildly affected individuals only receive attention after a more severely affected family member is identified. About 20-25% of DBA patients may be identified with a genetic test for mutations in the RPS19 gene.


Diamond and Blackfan described congenital hypoplastic anemia in 1938. In 1961, Diamond and colleagues presented longitudinal data on 30 patients and noted an associated with skeletal abnormalities. In 1997 a region on chromosome 19 was determined to carry a gene mutated in DBA. In 1999, mutations in the ribosomal protein S19 gene (RPS19) were found to be associated with disease in 42 of 172 DBA patients. In 2001, it was determined that a second DBA gene lies in a region of chromosome 8 although evidence for further genetic heterogeneity was uncovered.


Approximately 10-25% of DBA cases have a family history of disease, and most pedigrees suggest an autosomal dominant mode of inheritance. The disease is characterized by genetic heterogeneity, with current evidence supporting the existence of at least three genes mutated in DBA. In 1997, a patient was identified who carried a rare balanced chromosomal translocation involving chromosome 19 and the X chromosome. This suggested that the affected gene might lie in one of the two regions that were disrupted by this cytogenetic anomaly. Linkage analysis in affected families also implicated this region in disease, and led to the cloning of the first DBA gene. About 20-25% of DBA cases are caused by mutations in the ribosome protein S19 (RPS19) gene on chromosome 19 at cytogenetic position 19q13.2. Interestingly, some previously undiagnosed relatives of DBA patients were found to carry mutations. These patients also had increased adenosine deaminase levels in their red blood cells but no other overt signs of disease. A subsequent study of families with no evidence of RPS19 mutations determined that 18 of 38 families showed evidence for involvement of an unknown gene on chromosome 8 at 8p23.3-8p22. The precise genetic defect in these families has not yet been delineated. In a further 7 families, both the chromosome 19 and chromosome 8 loci could be excluded for involvement, suggesting the existence of at least one other DBA locus in the human genome.


[List your site here Free!]

Born to heal: screening embryos to treat siblings raises hopes, dilemmas
From Science News, 3/13/04 by Ben Harder

A decade later, pediatrician John E. Wagner still remembers the international phone call that led him to pioneer a new, controversial means to treat certain serious blood diseases. In his office at the University of Minnesota in Minneapolis, Wagner listened as a man living in Italy asked for help for his child, a victim of the genetic condition known as thalassemia. Having treated other young patients who had thalassemia, Wagner knew that healthy stem cells from either bone marrow or blood in an umbilical cord could mend the child's faulty circulatory system. The child would have the best shot at living a full life if the donated cells came from a sibling who had a genetically matched immune system.

The caller understood that. He and his wife were considering having another child. If naturally conceived, that child would have three chances in four of escaping thalassemia, and fertility doctors routinely improve those odds. Through genetic screening coupled with in vitro fertilization (IVF) techniques, which are also used to aid couples with fertility problems, doctors could load the dice such that the couple would be virtually certain to have a healthy child.

The caller knew all this too.

His questioning went one step further. If the geneticists could ensure that the new baby would be free of the gene for thalassemia, why couldn't they also boost the natural odds--one in four--that the next child would be an immune-matched donor for the child in need of the transplant?

They could, Wagner realized.

All the necessary medical technologies--IVF, screening of embryos for thalassemia and immune system genes, and transplantation of stem cells collected from umbilical cord blood--were available. They needed only to be used in combination.

"It was this father who put it together," Wagner says. Wagner, Mark Hughes of Wayne State University in Detroit, and their collaborators first successfully completed the combination of procedures in 2000. They performed IVF to create several embryos, selected and implanted into the womb an embryo that was both genetically healthy and immunologically matched to its sick sibling, and then, after that child was born, transplanted its made-to-match stem cells from the umbilical blood to the sibling.

Since then, more than a dozen sick children have been treated worldwide using the technique. The caller from Italy and his wife are among numerous couples attempting the same approach.

Those cases could be the vanguard of what's to come. Thousands of children with thalassemia, sickle-cell anemia, Fanconi anemia, various leukemias, and certain other circulatory conditions could benefit from the same innovative battery of procedures.

Wagner gets frequent inquiries about the approach from parents and doctors, but the cost dissuades many families from pursuing it. Ironically, using an immunologically matched sibling tends to lower the expense associated with stem cell transplantation, but the fertility steps needed to produce a matched donor are not covered by most health insurance plans, Wagner says.

Outside the United States, ethics laws that restrict the use of embryo screening pose obstacles to some families that might benefit from the therapeutic combination. In England, one case of screening for the sake of therapy has led to a protracted court battle.

No U.S. law makes such restrictions. But while that freedom has enabled medical pioneers to wield the lifesaving tool, Wagner is himself concerned about its vulnerability to abuse. By adding immunity-type screening to tests for genetic disease, he says, "we're moving to selection on the basis of a trait that is of no benefit to the child to be born. We're creating a donor."

With several colleagues, Wagner has recently proposed a framework for doctors and medical ethicists to use in deciding when the procedure is justified and how it should be conducted and regulated.

LOADING THE DICE "The concept [of selecting donors prenatally] is not new, but we've now got the technology," says Joe Leigh Simpson, an obstetrician and geneticist at Baylor College of Medicine in Houston. Doctors using other methods could determine a fetus' immunity type while the pregnancy is in progress and then abort any fetus that didn't match the ill sibling, he says. But that relatively crude approach is "dauntingly impractical," Simpson says.

A naturally conceived fetus in a family with a genetic disorder such as thalassemia has less than a 20 percent chance of being disease free and immunity matched. Simpson says, "You're going to end up aborting large numbers of pregnancies to get i what you want."

At the crux of the alternative, therapy-oriented embryonic i screening is a procedure known as preimplantation genetic diagnosis (PGD). First used in the late 1980s, it can be applied in any pregnancy involving IVF. The procedure is itself attracting attention in ethical and political circles. Some parents are using PGD to choose a child's sex. Some ethicists are concerned that the technology will eventually be used for choosing physical characteristics, such as eye color or height. They would consider that development as ethically indefensible.

The conventional, more widely accepted application for PGD is to enable a couple to eliminate the risk of passing a genetic disease to their child. Take Fanconi anemia, for example. In this disease, which occurs when a child inherits from both parents a particular mutation in a single gene, bone marrow fails to produce enough blood components.

Children born with Fanconi anemia die young unless they receive healthy, transplanted, blood-producing stem cells. More than 85 percent survive if they get stem cells from a sibling with whom they share the genes for a signature of the immune system called the human leukocyte antigen (HLA) type. Fewer survive when the HLA-matched donor is not a relative. Only about 18 percent survive with stem cells transplanted from an HLA-mismatched, unrelated donor. After having one child diagnosed with Fanconi anemia, a couple can use PGD to select an embryo with at least one normal copy of the implicated gene. Doctors would first perform IVF in the laboratory by fertilizing several eggs from a woman with sperm from her partner. Within a day, the nuclei of each pair of sperm and egg fuse to create a single-celled embryo, which incubates in a dish. The embryo then begins to divide, reaching the eight-cell stage after about 72 hours.

At that point, doctors use a laser to make a hole in the envelope surrounding the embryo and, with a pair of tiny pipettes, remove one cell in a procedure known as embryo biopsy. The seven-celled embryo, which is just as viable as an eight-celled one, remains in its dish while the biopsied cell is studied genetically.

When Wagner first used embryonic screening to produce an HLA-matched donor, it took 30 fertilized embryos to produce a baby with the right genetic makeup. But the infant, named Adam, saved his sister's life before he was a month old. Within minutes of his birth, doctors scooped up Adam's umbilical cord and carefully preserved the blood inside. Three weeks later, stem cells from that blood were transplanted into 6-year-old Molly, who suffered from Fanconi anemia. Today, both children are free of the disease, Wagner and his colleagues report in the February Blood.

The procedure can also be used to treat children with diseases, such as acute lymphoblastic leukemia, that are not inherited through simple genetics. In those cases, genetic screening isn't needed to prevent disease.

In the 4 years since Wagner's groundbreaking case, he and his colleagues have used embryonic screening to produce an HLA-matched stem cell donor for more than 30 other children. Four of these patients have received the transplant. For the others, who have less severe diseases, the stem cells have been stored for future use.

Demand for this novel approach to treatment is growing, says geneticist Yury Verlinsky. The Chicago-based Reproductive Genetics Institute, which Verlinsky runs, has conducted the PGD tests for nearly half of the approximately 1,000 children worldwide who were genetically screened as embryos since 1989, he says. That includes 8 children whose stem cells can heal a sibling, among them several of Wagner's patients. The treated diseases have included thalassemia, Fanconi anemia, Diamond-Blackfan anemia, Wiscott-Aldrich syndrome, and several other anemias and leukemias.

Another 12 women are pregnant with fetuses HLA-matched by the institute, and Verlinsky says he currently has 20 other cases at earlier stages in the process. He knows of one successful use of the procedure in Israel and efforts in Australia, Belgium, Turkey, and the United Kingdom.

With the volume of work it performs, Verlinsky's institute figures prominently in setting industry standards. Verlinsky eschews the use of PGD exclusively for sex selection and other purposes that are unrelated to the prevention or treatment of disease.

"I've had thousands of requests for the procedure," Wagner says. But few people actually go through with it once they understand the costs.

Because IVF and PGD are not typically covered by health insurance, few people can afford to attempt the procedure. Each round of IVF and PGD can cost $20,000, and expenses associated with stem cell transplantation, although sometimes covered, can run tens of thousands of dollars more. Multiple cycles of IVF and PGD are often needed to produce an HLA match. The first couple that attempted the procedure lost a son to Fanconi anemia after nine futile efforts to bear a stem cell donor for him, Wagner says.

Therapy-oriented genetic screening of embryos, when successful, lowers the overall cost of treating a child in need of stem cells when no HLA-matched relative is available. Patients receiving HLA-matched transplants tend to experience fewer complications and shorter hospital stays than those receiving unmatched transplants do, Wagner says.

LIFETIME COMMITMENT Unlike England, Australia, and some other countries, the United States has no governmental body that oversees uses of reproductive technologies. The foremost concern among U.S. doctors and ethicists considering HLA-matching PGD, Wagner says, is the potential risk to a deliberately conceived donor child.

Although the use of umbilical cord blood doesn't endanger the baby, transplants of other tissues may later be considered.

"This [child] is a perfect donor for life," Wagner says. If his or her cord blood fails to cure a sibling, parents might want the child to make contributions of bone marrow or even solid organs. These transplant procedures have risks to the donor.

To be sure that the costs and benefits to both siblings are taken into account, Wagner proposes that planned procedures be required to pass the ethical protocols used for human-subject research. He and two colleagues argued this position in the fall 2003 Journal of Law, Medicine, and Ethics.

Treating the HLA-matching PGD cases as experiments, thereby requiring oversight by medical institutions' ethics boards, will safeguard against doctors or parents favoring the interests of a sick child over those of a child-to-be, Wagner and his colleagues say.

For such deliberations, ethics reviewers would need to consider the severity of the sick child's condition, the intentions and psychological preparedness of the parents, and the possible physical and psychological burdens on the child-to-be. Wagner and his coauthors also argue that in each ease, an independent physician should be assigned to look out for the interests of the child-to-be.

According to Simpson, the ethical concerns surrounding therapy-oriented embryonic screening aren't completely novel. The only fresh twist is that they're manifested in the womb. Nevertheless, he says, "it's always wise to keep [PGD] under research protocols." The oversight of an institutional board also makes it more likely that doctors will later be able to use information about each ease in scientific studies, he says.

So far, no study has examined therapy-oriented screening for success rate, average cost, or effects on the donor. Those data will be vital for doctors and parents considering the therapy in the future.

COPYRIGHT 2004 Science Service, Inc.
COPYRIGHT 2004 Gale Group

Return to Anemia, Diamond-Blackfan
Home Contact Resources Exchange Links ebay