Congenital Dyserythropoietic Anemia Type 1

The parents of a six-month-old male infant complained that the child had developed a fever over the last three days after an episode of paleness, which persisted for the last 20 days. 

The baby was the firstborn from his non-consanguineous parents. There was no history of recent bleeding episodes or prior blood transfusions. The child was exclusively breastfed and showed regular developmental progress. 

Physical examination revealed a body weight of 6 kg, length - 64 cm, and head circumference - 42 cm. His vitals showed – a heart rate of 140 beats per minute, respiratory rate of 42 breaths per minute, facial puffiness, peripheral edema, and evident pallor. Abdominal examination revealed non-tender, soft hepatomegaly with a liver span of 7 cm and without splenomegaly. Other systemic examinations appeared normal.

Laboratory investigations showed:

• Hemoglobin level - 2.8 g/dl
• Red blood cell count (RBC) - 0.76 million cells/microliter
• White blood cell (WBC) count - 16,700 cells/microliter
• Platelet count - 115,000 cells/microliter
• Mean corpuscular volume (MCV) - 94 femtoliters 

A peripheral blood smear indicated anisopoikilocytosis, primarily with normocytic normochromic RBCs, displaying macrocytosis. Liver function tests showed:

• Serum total bilirubin - 2.70 mg/dl
• Unconjugated bilirubin - 1.6 mg/dl
• AST - 60 U/L
• ALT - 17 U/L
• Alkaline phosphatase - 83 U/L

Serum electrolytes and creatinine levels were within the normal range. Serum ferritin levels were elevated at 975 ng/dl, and the reticulocyte count was 12.5, with a corrected reticulocyte count of 2.4%. Vitamin B12 deficiency was excluded. High-performance liquid chromatography testing for hemoglobinopathies returned negative results. Abdominal ultrasonography did not reveal gallstones.

Subsequent bone marrow examination showed hypercellularity with erythroid hyperplasia. Erythropoiesis displayed megaloblastic characteristics, such as nuclear budding, micronuclei, multinuclearity, and multipolar mitosis. Erythroblasts exhibited chromatin bridges, with occasional red blood cells showing basophilic stippling. 

The findings led to the diagnosis of congenital dyserythropoietic anemia. The acidified serum lysis test (HEMPAS) yielded negative results, and genetic studies were unavailable. The diagnosis of CDA type 1 was made based on the early age of presentation, the presence of megaloblastic cells on the peripheral smear, internuclear chromatin bridges between erythroblasts on bone marrow examination, and the negative HEMPAS test. 

The infant received packed red cell transfusions and symptomatic treatment. Following discharge, the child continued to be monitored and required further transfusions during follow-up. 

CDA 1 should be considered in cases of refractory anemia, hepatosplenomegaly, erythroid hyperplasia, and features of dyserythropoiesis observed in marrow examinations. Hyperbilirubinemia and unexplained iron overload should also raise suspicion of CDAs. The diagnosis of CDA 1 can be based on typical characteristics observed in peripheral blood smears and bone marrow examinations.

Source: Chandel AS, Itihas A, Jategaonkar S, Jain M, Paediatrics MS. NIJP. 2019 Oct;8:4.