Diagnosis

Diamond Blackfan anemia (DBA) was first recognized as a distinct entity in 1938. The accepted diagnostic criteria for DBA published in 1976 were:

  1. usually macrocytic anemia (a decreased number of larger than normal red blood cells)

  2. reticulocytopenia (a decreased number of new, young red blood cells)

  3. normal bone marrow cellularity with a selective deficiency in red blood cell precursors

  4. normal or slightly decreased white blood cell count

  5. normal or slightly increased platelet count

DIAGNOSTIC CRITERIA

  • Age less than 1 year at presentation of anemia

  • Anemia defined as low hemoglobin for age with macrocytic (large red cell size) or normocytic (normal red cell size) cells with no other significant cytopenias (relatively normal white cell and platelet numbers)

  • Reticulocytopenia (low numbers of red cell precursors)

  • Normal bone marrow cellularity with a selective deficiency of red cell precursors

Supporting Criteria

Major

  • Positive family history

  • Ribosomal protein (RP) gene or GATA1 mutation identified

​Minor

  • Elevated erythrocyte adenosine deaminase activity (eADA; a red cell enzyme found to be elevated in 85% of DBA patients)

  • Presence of birth defects (found in about 50% of DBA patients)

  • Elevated fetal hemoglobin (a type of hemoglobin seen in infancy but found in DBA patients after infancy)

  • No evidence of another inherited bone marrow failure syndrome

A diagnosis of classical DBA is made if all the diagnostic criteria are present. If not all the diagnostic criteria are met then an otherwise normal individual is considered as having non-classical DBA if he/she has the same RP or GATA1 mutation as the DBA patient. 

A person can be assigned as having a “probable” diagnosis of DBA if:

  • 3 diagnostic criteria are present along with a positive family history; or

  • 2 diagnostic criteria and 3 minor supporting criteria are present; or

  • positive family history and 3 minor supporting criteria are evident

What causes DBA?​

Although a number of theories regarding the pathophysiology (cause) of DBA have been proposed, it is now widely accepted that the disorder results from a problem within the early immature red cells that makes them highly sensitive to death by apoptosis (which is a specific type of programmed cell death). It has now been shown that DBA is caused by mutations in ribosomal protein (or RP) genes. The first DBA gene identified was RPS19, one of the 80 known RP genes. The existence of mutations in genes encoding similar ribosomal proteins and other non-ribosomal protein gene mutations (such as GATA1) has been confirmed. The functions of these proteins in DBA are not yet well understood. Studies are underway to identify gene mutations in the approximately 30% of patients with DBA for whom no genetic cause has been identified.

Small variants in the coding sequence of 12 ribosomal protein genes are responsible for 55-60% of DBA cases. Ribosomal protein gene deletions leading to haplo insufficiency of these comprise an additional 10% of cases. The genetic basis for the remaining cases remains unknown. A few families have been described to have a GATA1 mutation, thus a non-RP gene has been implicated in DBA as well.

Diamond Blackfan anemia is the preferred name for this disorder but other terms for DBA have included:

 

• Blackfan Diamond anemia
• congenital pure red cell aplasia
• congenital hypoplastic anemia
• Aase syndrome (which is now felt to be a subset of DBA and not a distinct disorder)

INCIDENCE

Incidence is estimated at 5-10 cases for every million children born in the United States and Canada.  We estimate about 20-40 new cases per year in the United States and Canada.  There are an equal number of males and females with the disease.  Children usually appear to be affected with anemia by 2 months of age with a range from birth to 6 years. 93% of the patients present with anemia during the first year of life.  The diagnosis of DBA is generally made at 3 months of age with a range from birth to adulthood.

It is important to note that more and more adults are being diagnosed with DBA:

 

  • Some patients may present with mild anemia and become more severe later in life.

  • Sometimes a parent is diagnosed after his/her child is diagnosed with DBA and the gene is found in the parent and the child.

  • Family members without anemia may have congenital anomalies and then found to have the DBA gene once their relative is diagnosed with DBA.