Severe hereditary spherocytosis presenting with non-immune fetal hydrops

Background: Hereditary spherocytosis (HS) is characterized by spherocytes on the peripheral smear and heterogeneous clinical presentation (mild, moderate, moderate/severe, and severe) depending upon the severity of hemolytic anemia, jaundice, and splenomegaly. The underlying cause is defects in various red blood cell membrane proteins due to pathogenic mutations. Genotype-phenotype correlation is known. Clinical Description: We report a consanguineous family with a healthy daughter, multiple pregnancy losses due to fetal hydrops, and the current daughter. She was diagnosed with fetal anemia at 22 weeks gestation, developed fetal hydrops, was born premature and developed respiratory distress, severe anemia, severe jaundice, and postnatal hemolysis. Management: The case was managed since intrauterine life till date by multispecialty coordination. Intrauterine transfusions were given during pregnancy. In the neonatal period, she received surfactant for respiratory distress syndrome, double volume exchange transfusion and phototherapy for the jaundice, and repeated blood transfusions for the hemolytic anemia, that is still continuing. Rational and sequential investigations were planned and a systematic approach used. She was diagnosed with severe HS due to a homozygous likely pathogenic variant in the SPTA1 gene (affecting formation of spectrin), and heterozygous variant of uncertain significance in the ANK1 gene (that encodes ankyrin). At 3 years she has transfusion dependent hemolytic anemia, moderate splenomegaly, and age appropriate growth and development. Conclusions: HS is a rare but manageable (albeit challenging) cause of nonimmune hydrops fetalis. Genetic diagnosis allows precise management and family counselling.