21 genes: RPS19, RPL5, RPS26, RPL11, RPL35A, RPS10, RPS17, RPS24, GATA1, RPL15, RPL18, RPL26, RPL27, RPL31, RPL35, RPS7, RPS15A, RPS27, RPS28, RPS29, TSR2
Also known as: Congenital erythroid hypoplastic anaemia; Hereditary pure red cell aplasia, Chronic congenital aregenerative anaemia; erythrogenesis imperfecta; AASE-Smith syndrome II; AASE syndrome
Includes:
– OMIM#105650 https://omim.org/entry/105650
– OMIM#610629 https://omim.org/entry/610629
– OMIM#612561 https://omim.org/entry/612561
– OMIM#613309 https://omim.org/entry/613309
– OMIM#612562 https://omim.org/entry/612562
– OMIM#612528 https://omim.org/entry/612528
– OMIM#613308 https://omim.org/entry/613308
– OMIM#612527 https://omim.org/entry/612527
– OMIM#300835 https://omim.org/entry/300835
– OMIM#615550 https://omim.org/entry/615550
– OMIM#618310 https://omim.org/entry/618310
– OMIM#614900 https://omim.org/entry/614900
– OMIM#617408 https://omim.org/entry/617408
– OMIM#618312 https://omim.org/entry/618312
– OMIM#612563 https://omim.org/entry/612563
– OMIM#618313 https://omim.org/entry/618313
– OMIM#606164 https://omim.org/entry/606164
– OMIM#615909 https://omim.org/entry/615909
– OMIM#300946 https://omim.org/entry/300946
1. The disease:
Diamond-Blackfan anaemia (DBA) is characterized by a profound normochromic and usually macrocytic anemia with normal leukocytes and platelets.
2. The symptoms:
The anaemia is discovered early in life, usually within the first 2 years; diagnosis after 4 years of age is very unlikely.
- Pallor and dyspnoea, especially during feeding or while sucking, are the principal warning signs. Pallor is isolated, without organomegaly, signs suggestive of hemolysis or involvement of other hematopoietic cell lines. The hematologic complications occur in 90% of affected individuals during the first year of life.
- Over half of all DBA patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies.
- The phenotypic spectrum ranges from a mild form (e.g., mild anaemia or no anaemia with only subtle erythroid abnormalities, physical malformations without anaemia) to a severe form of foetal anaemia resulting in nonimmune hydrops fetalis. DBA is associated with an increased risk for acute myelogenous leukaemia (AML), myelodysplastic syndrome (MDS), and solid tumours including osteogenic sarcoma.
3. Actions to take in case of early diagnosis:
- Correlation with laboratorial findings as macrocytic anaemia with onset prior to age one year, no other significant cytopenias, reticulocytopenia, normal marrow cellularity with a paucity of erythroid precursors can help in the diagnosis.
- DBA is a lifelong disease requiring lifetime management and regular follow-up with a Haematology Center. Management is provided by multidisciplinary team.
- Corticosteroid treatment, recommended in children older than age 12 months, improves the red blood cell count in approximately 80% of affected individuals.
- Chronic transfusion with packed red blood cells is necessary during the first year of life to avoid steroid-induced toxicity in those not responsive to a trial of corticosteroids at age 12 months and in individuals who relapse.
- Hematopoietic stem cell transplantation (HSCT), the only curative therapy for the hematologic manifestations of DBA, is often recommended for those who are transfusion dependent or develop other cytopenias.
- Ocular, skeletal, genitourinary, cardiac, and endocrine complications are best managed in collaboration with appropriate subspecialists from the multidisciplinary team.
- Agents/circumstances to avoid: Deferiprone for the treatment of iron overload (which can cause neutropenia); infection (especially in individuals on corticosteroids).
- Genetic counselling should be offered to at-risk family members.
4. For more information:
Biblio : https://www.ncbi.nlm.nih.gov/books/NBK7047/