PC2158: A Rare Cause of Severe Hyperbilirubinemia in a Late Preterm Infant

Introduction: Neonatal jaundice is a condition affecting nearly 10% of infants. Hyperbilirubinemia requiring further intervention in the newborn period is commonly caused by: physiologic jaundice, breastfeeding jaundice, or isoimmune hemolytic disease. We present a case of severe hyperbilirubinemia in the newborn secondary to a rare hereditary red blood cell membrane cation defect.

Case Description: Initially admitted to the neonatal intensive care unit (NICU) for hypoglycemia, an 36+6 week female infant was noted to be profoundly jaundiced. Laboratory evaluation confirmed hyperbilirubinemia of 14.6 mg/dL at 16 hours of life.

Additional lab analysis revealed a hematocrit of 39.9% ,23% reticulocytes and a white blood cell count of 34 k/uL with an immature-to-total neutrophil ratio of 0.24. Direct antigen testing was negative. Peripheral blood smear revealed marked stomatocytosis. Red blood cell (RBC) indices showed markedly elevated mean corpuscular volume and mean corpuscular hemoglobin, with decreased mean corpuscular hemoglobin concentration. The infant was started on phototherapy, intravenous (IV) fluids, and antibiotics. At the time of admission, a review of maternal history revealed a maternal diagnosis of stomatocytosis.

The infant’s bilirubin trended downward while on phototherapy and IV fluids. She remained otherwise well with no additional signs of infection and was able to discontinue phototherapy on day of life 4. She was discharged from the NICU on day of life 5 on folate supplementation and followed up with pediatric hematology as an outpatient with the presumptive diagnosis of hereditary stomatocytosis. Since her NICU discharge, she has required three packed RBC transfusions

Discussion: Hereditary stomatocytosis (HSt) is an autosomal dominant family of red blood cell disorders caused by abnormal permeability to sodium and potassium ions.

The four subgroups of HSt are, in descending order of frequency: dehydrated HSt, overhydrated HSt, cryohydrocytosis, and familial pseudohyperkalemia. Clinically, these subgroups represent a spectrum of disease ranging from mild to severe hemolysis. This can present as anemia and jaundice.

Our patient’s laboratory values are most consistent with a diagnosis of overhydrated hereditary stomatocytosis (OHSt). The overhydrated phenotype is caused by increased monovalent cation leak in the setting of absent stomatin. As a result, there is excess cation leak with increased intracellular water content. The resultant cells are large and osmotically fragile. The red blood cell indices associated with this phenotype are: decreased mean corpuscular hemoglobin concentration, macrocytosis, elevated mean corpuscular hemoglobin, and a positive osmotic fragility test.

Conclusion: While isoimmune hemolytic disease leading to jaudnice is common in the newborn period, a high index of suspicion for non immune-mediated hemolysis should remain in infants with pathologic jaundice without evidence of an isoimmune process. Our case highlights a rare red blood cell cation defect resulting in hemolysis and jaundice.