Discussion
This patient presented with congenital anemia of unknown cause with a
history of intrauterine transfusion requirement. Hemolytic markers were
strikingly elevated. Reticulocytosis explained the high MCV. The
differential diagnosis of congenital hemolytic anemia is wide
(supplemental table 2). Maternal-fetal alloimmunization is the most
common etiology. There are case reports of fetuses with hydrops fetalis
secondary to alloimmunization that were born with a negative IAT (17).
We therefore performed extensive blood bank testing that completely rule
out alloimmunization. We sent a mucosal DNA NGS inherited hemolytic
anemia panel. This test is not affected by the post-transfusion status.
CDA was historically diagnosed by RBC property testing and bone marrow
morphology. However, with the advent of genetic testing, NGS has become
the gold standard to diagnose rare congenital hemolytic anemia, like
CDA. The genetic basis of CDAIV was first sequenced nearly ten years ago
by Arnaud & al. (2010), who identified two patients with a KLF1
mutation. Twelve patients have been described since. Most show
consistent features with onset in the neonatal period (8/12 patients),
but delayed diagnoses occur despite accessible technologies (see table
1). We reached a diagnosis within one month of life, which is the
fastest CDA diagnosis ever described. In summary, our case highlights a
patient with CDA4 de novo mutation with in uteroerythropoietic disturbances requiring transfusion, post-natal hemolytic
anemia and combined hyperbilirubinemia transiently refractory to
exchange transfusions. Thrombocytopenia has been rarely described in
CDAI and CDAIV(18). The transient thrombocytopenia of this patient was
considered secondary to exchange transfusions. This case demonstrates
the importance of a prenatal referral to hematology and neonatology when
hydrops fetalis of unknown etiology is detected for diagnostic and
postnatal planning purposes. It is a reminder that it is optimal
practice to obtain pre-transfusion blood sampling in an EDTA tube in
patients with severe anemia. Finally, it illustrates that the use of NGS
technologies can expedite early diagnosis of rare congenital anemia,
like CDAIV, allows for anticipatory guidance and consequently reduces
anxiety of clinicians and families, while optimizing health care
utilization.