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.