Introduction
Congenital dyserythropoietic anemia (CDA) is an aggregation of rare inherited hematological disorders characterized by a hallmark feature of altered erythropoiesis. CDA can be subdivided into 5 categories, namely type I, II, III, transcription factor related CDA and CDA variants(1). Each type is characterized by varying hematopathological findings, clinical presentation, and underlying genetic basis (1). CDAIV (Online Mendelian Inheritance in Man (OMIM): 613673) is part of the transcription factor-related CDA family and accounts for only 0.4% of all patients with CDA (1). To date, 12 patients have been identified with CDAIV (see table 1). Patients are found to have a mutation in the transcription factor KLF1, which has been implicated in various mild hematological disorders (see supplemental table 1) (2). This is likely due to the KLF1 role at multiple levels of the erythropoietic process, and varying mutations may lead to different functional consequences on the transcription factor (3-5). CDAIV is an autosomal dominant condition in which most patients harbour a de novo heterozygous mutation c.973G.A (p.E325K) (see table 1) (3-5). Most CDAIV patients present severe anemia, hemolysis, hepatosplenomegaly, hyperbilirubinemia, and persistence of fetal hemoglobin. They are often transiently transfusion-dependant. Many patients present in the neonatal period but are only diagnosed later in life, because of the non-specific symptomatology of hemolytic anemias.
We present a case of CDAIV, which presented with severe neonatal anemia and hyperbilirubinemia, with a subsequent rapid diagnosis through a commercially available next-generation sequencing (NGS) panel for congenital hemolytic anemias. We highlight the importance of considering early genetic testing for unexplained severe and refractory congenital anemias. Additionally, we advocate for pre-transfusion blood storage in cases of unexplained anemia in newborns to prevent delays in diagnosis due to the presence of circulating donor’s RBC. Of note, we remind clinicians that it is routine practice for laboratories to store pre-transfusion blood samples for 1 week.