Double Heterozygous Mutation with a Likely Pathogenic Variant and a VUS in SEC23B Gene: A Diagnostic Challenge for Congenital Dyserythropoietic Anemia in a Child – A Case Report

Abstract Background: Congenital dyserythropoietic anemia (CDA) is a rare cause of inherited transfusion-dependent anemia. Here, we describe the diagnostic complexity, which was enhanced due to a superimposed parvovirus infection, compounded further by difficulty in interpreting genetic sequencing results. Clinical Description: A 1-year-old girl presented with acute paleness and fever, having a history of repeated transfusions; family history being unremarkable. Examination revealed moderate malnutrition, pallor, mild icterus, and hemolytic facies with marked hepatosplenomegaly. Management and Outcome: Investigations showed macrocytic anemia, raised bilirubin, with reticulocytopenia; other cell lines being normal. Hemoglobinopathies and other common hemolytic anemias were ruled out. Bone marrow showed erythroid hyperplasia with dyserythropiesis. Parvovirus B19 was positive, but could not explain chronic hemolysis. Gene sequencing showed two variants in SEC23B , one of them being a variant of uncertain significance. Segregation analysis of the mother and phenotypic correlation confirmed the diagnosis. Conclusion: The case here portrays the diagnostic challenges faced while working-up a child presenting with chronic transfusion-dependent anemia. Even genetic sequencing may not give straightforward answers, underscoring the need for a background knowledge of CDA and astute clinical work-up.