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Disease Profile

Diamond-Blackfan anemia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

US Estimated

Europe Estimated

Age of onset

Infancy

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ICD-10

D61.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

DBA; Anemia Diamond Blackfan type; Blackfan Diamond syndrome;

Categories

Blood Diseases; Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases;

Summary

Diamond-Blackfan anemia is an inherited blood disorder that affects the ability of the bone marrow to produce red blood cells.[1] Symptoms may include a shortage of red blood cells (anemia), physical abnormalities such as small head size (microcephaly) characteristic facial features, cleft palate, cleft lip, short and webbed neck, small shoulder blades, and defects of the hands (mostly of the thumbs), as well as defects of the genitalia, urinary tract, eyes and heart. In some cases there is also short stature.[2]

Diamond-Blackfan anemia is caused by mutations in several genes, some of which have been identified and some of which have not. Identified genes include but are not limited to: RPS19, RPL5, RPS10, RPL11, RPL35A, RPS7, RPS17, RPS24, RPS26 and GATA1 genes. Different subtypes exist and are divided based on the specific gene mutated; however, they have similar features. Patients with mutations in the RPL5 gene have more serious symptoms and about 45% have cleft palate and are smaller than average size. Patients with mutations in the RPL11 gene have thumb anomalies more frequently than people with the other types. Mutations in the GATA1 gene are associated with severe anemia.[3][4] Most cases are isolated, but about 45% of people with Diamond-Blackfan anemia inherit this condition from a parent. Inheritance is typically autosomal dominant , but can rarely be X-linked.[3]

Treatment may involve corticosteroids, blood transfusions, a bone marrow transplant or stem cell transplantation.[1] The severity of the disease is very varied. People with Diamond-Blackfan anemia may have an increased risk of having diseases related to a bone marrow defect, such as myelodysplastic syndrome, and certain cancers.[3][2] Adults with the disease may have hormonal problems in later life, specially adrenal insufficiency, hypogonadism and hypothyroidism.[5] 

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Elevated red cell adenosine deaminase level
0030270
Pure red cell aplasia
0012410
30%-79% of people have these symptoms
Erythroid hypoplasia
0012133
Increased mean corpuscular volume
0005518
Lethargy
0001254
Macrocytic dyserythropoietic anemia
0005532
Pallor
0000980
Persistence of hemoglobin F
0011904
Reticulocytopenia
0001896
Small for gestational age
Birth weight less than 10th percentile
Low birth weight

[ more ]

 0001518
5%-29% of people have these symptoms
Abnormality of the thenar eminence
0001227
Absent thumb
Absent thumbs
0009777
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

 0001631
Cleft lip
0410030
Cleft soft palate
0000185
High palate
Elevated palate
Increased palatal height

[ more ]

 0000218
Horseshoe kidney
Horseshoe kidneys
0000085
Hypospadias
0000047
Leukopenia
Decreased blood leukocyte number
Low white blood cell count

[ more ]

 0001882
Myelodysplasia
0002863
Neurodevelopmental delay
0012758
Normochromic anemia
0001895
Partial duplication of thumb phalanx
Partial duplication of the thumb bones
0009944
Radial artery aplasia
0020118
Renal agenesis
Absent kidney
Missing kidney

[ more ]

 0000104
Short neck
Decreased length of neck
0000470
Short stature
Decreased body height
Small stature

[ more ]

 0004322
Short thumb
Short thumbs
Small thumbs

[ more ]

 0009778
Sprengel anomaly
High shoulder blade
0000912
Triphalangeal thumb
Finger-like thumb
0001199
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Webbed neck
Neck webbing
0000465
1%-4% of people have these symptoms
Acute myeloid leukemia
0004808
Adenocarcinoma of the colon
0040276
Coarctation of aorta
Narrowing of aorta
Narrowing of the aorta

[ more ]

 0001680
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

 0005280
Developmental cataract
Clouding of the lens of the eye at birth
0000519
Developmental glaucoma
0001087
Epicanthus
Eye folds
Prominent eye folds

[ more ]

 0000286
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

 0000316
Low anterior hairline
Low frontal hairline
Low-set frontal hairline

[ more ]

 0000294
Low-set ears
Low set ears
Lowset ears

[ more ]

 0000369
Malignant genitourinary tract tumor
0006758
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

 0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

 0000347
Microtia
Small ears
Underdeveloped ears

[ more ]

 0008551
Neutropenia
Low blood neutrophil count
Low neutrophil count

[ more ]

 0001875
Nonimmune hydrops fetalis
0001790
Osteosarcoma
Bone cell cancer
0002669
Ptosis
Drooping upper eyelid
0000508
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

 0000486
Thrombocytopenia
Low platelet count
0001873
Thrombocytosis
Increased number of platelets in blood
0001894
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

 0000431
Do you have updated information on this disease? We want to hear from you.

Cause

Diamond-Blackfan anemia (DBA) can be caused by mutations in the RPS19 gene (25% of the cases) or in the following genes: RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, or RPS26 genes (25%-35% of the cases). In very rare cases, the disease is caused by a mutation in the GATA1 gene. In the remaining 40%-50% of the cases the cause is unknown.[3][2]

The RPS19, RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, and RPS26 genes provide instructions for making several of the different ribosomal proteins. Ribosomes are components of cellular structure that process the cell's genetic instructions to create proteins. Each ribosome is made up of two parts (subunits) called the large and small subunits. The RPL5, RPL11, and RPL35A genes provide instructions for making ribosomal proteins found in the large subunit. The ribosomal proteins produced from the RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 genes are among those found in the small subunit. Some ribosomal proteins are involved in the assembly or stability of ribosomes and others help building new proteins or have other functions. A shortage of functioning ribosomal proteins may increase the self-destruction of blood-forming cells in the bone marrow, resulting in anemia.[3][2]

According to the mutated gene people may have some differences in their symptoms:[6][7]

  • People who have mutation in the RPL5 gene appear to have more severe problems than people with mutations in the RPL11 and RPS19 genes.
  • People with mutations in the RPL5 gene have more chances of having cleft lip and/or cleft palate defects.
  • People with mutations in the RPL11 gene have more thumb abnormalities 
  • People with mutations in the GATA1 gene may have a more severe anemia.

In about 30% of people diagnosed with Diamond-Blackfan anemia no mutation is found in any of the known DBA-linked genes.[6]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    Some people have such mild signs and symptoms that they do not require treatment. In people who require treatment it may include:[3]

    • Corticosteroids: Corticosteroid treatment is recommended in children over 1 year of age; this treatment can initially improve the red blood count in approximately 80% of people with Diamond-Blackfan anemia. Prednisone initial dose is 2 mg / kg / day given orally once a day, at morning time. After a month, if there is no improvement after a month the corticosteroids are tapered-of and suspended
    • Blood transfusions, which are given along with the corticosteroids or in people who do not get better with corticosteroids
    • Bone marrow/stem cell transplantation: It is the only curative treatment for the anemia; however, patients should continue to be followed because they are at increased risk for leukemia and cancer. Results are better for children younger than ten years of age if transplanted using an Human Leukocyte Antigen (HLA)-matched sib

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • The Children's Hospital Boston provides an information page on Diamond-Blackfan anemia. Click on the link above to access this information.
      • Genetics Home Reference (GHR) contains information on Diamond-Blackfan anemia. This website is maintained by the National Library of Medicine.
      • The National Cancer Institute provides the most current information on cancer for patients, health professionals, and the general public.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Diamond-Blackfan anemia in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Diamond-Blackfan anemia. Click on the link to view a sample search on this topic.

          Selected Full-Text Journal Articles

            References

            1. Diamond Blackfan Anemia. Centers for Disease Control and Prevention (CDC). 2015; https://www.cdc.gov/ncbddd/dba/facts.html.
            2. Diamond-Blackfan anemia. Genetics Home Reference. November 2015; https://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia.
            3. Clinton, C & Gazda, HT. Diamond Blackfan Anemia. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/books/NBK7047/.
            4. Diamond-Blackfan Anemia. Online Mendelian Inheritance in Man (OMIM). 2017; https://omim.org/entry/105650.
            5. Muir C, Dodds A & Samaras K. Mid-life extra-haematopoetic manifestations of Diamond–Blackfan anaemia. Endocrinology, Diabetes & Metabolism Case Reports. 2017; 2017:16-0141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409934/.
            6. Da Costa L, O'Donohue MF, van Dooijeweert B et al. Molecular approaches to diagnose Diamond-Blackfan anemia: The EuroDBA experience. Eur J Med Genet. October 26, 2017; 1769-7212(17):30505-0. https://www.ncbi.nlm.nih.gov/pubmed/29081386.
            7. Diamond-Blackfan anemia 6. OMIM. 2016; https://omim.org/entry/612561.

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