EP18.15: Non‐immune fetal hydrops due to severe fetal anemia in a fetus with mutations in the alpha‐spectrin SPTA1 gene: a case report

Hereditary Spherocytosis (HS) is one of the most common inherited anemias. It typically due to autosomal dominant inheritance though some cases are inherited in an autosomal recessive pattern. HS is caused by abnormal production of red blood cell membrane proteins resulting in atypical spherical cell shape. It typically causes mild-moderate anemia, jaundice, and splenomegaly. The severe form of the condition is rare and can cause potentially lethal non-immune hydrops fetalis. We report a 19-year-old woman G2P1 who presented at 21 weeks due to a pericardial effusion. Two weeks later, the fetus was noted to be hydropic with a pericardial effusion, ascites, and polyhydramnios. The patient had an obstetric history significant for intrauterine fetal demise secondary to fetal hydrops at 20 weeks. Evaluation of the middle cerebral artery Doppler demonstrated an elevated peak systolic velocity concerning for severe fetal anemia. Percutaneous umbilical blood sampling revealed a fetal hematocrit of 6%. Throughout the pregnancy, the patient required six intrauterine transfusions. A prenatal hydrops gene panel identified two variants in the alpha-spectrin gene, SPTA1 [likely pathogenic variant c.2671C>T; p.Arg891*, and a variant of uncertain clinical significance c.3841C>G; p.Arg1281Gly]. Postnatally, the infant was transfusion dependent every 2 weeks. Further analysis of the SPTA1 gene identified the two known variants from the prenatal studies in addition to a novel splice site mediating variant in the gene. Two of these variants were inherited in a single copy of the gene from the mother and the other variant inherited in trans from her father, thus confirming the diagnosis of severe autosomal recessive or non-dominant hereditary spherocytosis (ndHS) due to compound heterozygous mutations of alpha-spectrin production. This case highlights the importance of considering autosomal recessive HS or ndHS in patients presenting with non-immune fetal hydrops due to severe fetal anemia.