Gilbert's syndrome coexisting with hereditary spherocytosis might not be rare: Six case reports

Abstract

Background: Both Gilbert's syndrome (GS) and hereditary spherocytosis (HS) are common genetic disorders. However, comorbidity of GS with HS has always been considered a rare phenomenon, and it can impede accurate diagnoses in the presence of isolated unconjugated hyperbilirubinemia.

Case summary: In a study on Levitt's carbon monoxide (CO) breath test for the differential diagnosis of isolated hyperbilirubinemia, we found six GS patients with HS in 6 mo. The patients, including five males and one female, aged 25-58 years, were from four families and generally in good health. Their chronic fluctuating jaundice and/or hyperbilirubinemia had been diagnosed as simple constitutional jaundice for 6-30 years. Liver function tests showed isolated unconjugated hyperbilirubinemia with serum total bilirubin ranging from 20.7-75.4 μmol/L. Blood hemoglobin was normal in five cases, and slightly decreased in one (11.5 g/dL). Overt hemolytic signs were absent, while erythrocyte lifespan determined by the newly developed Levitt's CO breath test was significantly short (15-50 d), definitely demonstrating the presence of hemolysis. Given that their unconjugated hyperbilirubinemia compared inappropriately with hemolytic severity, as indicated by the hemoglobin level, further combined genetic tests for both UGT1A1 and hereditary erythrocyte deficiencies were conducted. These tests confirmed, at last, the coexistence of GS with HS.

Conclusion: Comorbidity of GS and HS might not be uncommon in isolated unconjugated hyperbilirubinemia. While CO breath test would sensitively detect the hemolysis, the discordance between the hyperbilirubinemia and hemoglobin level could strongly indicate the coexistence of GS and HS.

Keywords: Case report; Erythrocyte lifespan; Gilbert’s syndrome; Hereditary spherocytosis; Levitt’s CO breath test; Unconjugated hyperbilirubinemia.