From the Guidelines
Diamond-Blackfan syndrome, also known as Diamond-Blackfan anemia (DBA), is a rare congenital bone marrow failure disorder characterized by a failure to produce red blood cells, associated with congenital malformations, impaired growth, and an increased risk of malignancy, particularly myelodysplastic syndrome (MDS) and solid tumors such as osteosarcoma and colon cancer. This condition is typically presenting with red cell aplasia, and associated features include congenital malformations in about 50% of cases, most commonly craniofacial, upper extremity, cardiac, and genitourinary, and impaired growth 1. DBA is primarily caused by germline heterozygous variants in one of 24 genes coding for small or large ribosomal proteins, with more than half of cases due to de novo variants 1. Some key points to consider in the management of DBA include:
- Regular monitoring of blood counts, growth, development, and screening for associated malformations and malignancies is essential for comprehensive management of this lifelong condition.
- An international consensus of experts now recommends colonoscopy beginning at 20 years of age in addition to hematologic surveillance 1.
- The risk of developing malignancy in individuals with DBA is significant, with a cumulative incidence of 13.7% by the age of 45 years, highlighting the need for close surveillance and monitoring 1.
- Treatment typically involves corticosteroids, with prednisone being a common first-line therapy, and hematopoietic stem cell transplantation is the only curative option and should be considered for transfusion-dependent patients with a suitable donor.
From the Research
Definition and Characteristics
- Diamond-Blackfan anemia (DBA) is a rare constitutional inherited bone marrow failure syndrome (iBMF) characterized by progressive severe non-regenerative anemia and congenital abnormalities 2.
- It is a rare genetic disorder affecting the bone marrow's ability to produce red blood cells, leading to severe anemia and various physical abnormalities 3.
- DBA is an inherited bone marrow failure syndrome, characterized as a rare congenital bone marrow erythroid hypoplasia 4.
Causes and Genetics
- Diagnosis is made by identification of a DBA-causing variant, typically in a ribosomal protein gene 2.
- Approximately 75% of DBA cases involve heterozygous mutations in ribosomal protein (RP) genes, classifying it as a ribosomopathy, with RPS19 being the most frequently mutated gene 3.
- DBA is due to a defect in the ribosomal RNA (rRNA) maturation as a consequence of a heterozygous mutation in 1 of the 20 ribosomal protein genes 4.
Clinical Features and Diagnosis
- Erythroid defect in DBA results in erythroblastopenia in bone marrow as a consequence of maturation blockade between the burst forming unit-erythroid and colony forming unit-erythroid developmental stages, leading to moderate to severe usually macrocytic aregenerative anemia 4.
- Congenital malformations localized mostly in the cephalic area and in the extremities (thumbs), as well as short stature and cardiac and urogenital tract abnormalities, are a feature of 50% of the DBA-affected patients 4.
- Assessment of biological features in conjunction with genetic testing has increased the accuracy of the diagnosis of DBA 5.
Treatment and Management
- Current treatment options are either regular transfusions with appropriate iron chelation or treatment with corticosteroids starting at 1 year of age 4.
- The only curative treatment for the anemia of DBA to date is bone marrow transplantation 4.
- Gene therapy, particularly using lentiviral vectors and CRISPR/Cas9 technology, emerges as a promising alternative 3.