Beyond Gilbert's syndrome: hyperbilirubinaemia due to combined UGT1A1 mutation associated with an ATP11C variant

Gilbert syndrome (GS) is the main cause of benign unconjugated hyperbilirubinaemia. However, total bilirubin levels higher than those usually observed in GS, or the presence of associated haematological features, should prompt consideration of additional genetic contributors. We report a case of persistent hyperbilirubinaemia in a patient previously diagnosed with GS whose biochemical profile was not entirely consistent with the expected phenotype. Clinical exome identified a very unusual combined UGT1A1 mutation associated with an ATP11C variant, providing a plausible explanation for the atypical laboratory findings. This report illustrates the potential complexity underlying hereditary hyperbilirubinaemia, highlights the diagnostic value of clinical exome in GS patients with atypical biochemical or haematological findings and expands the phenotypic spectrum of ATP11C-related disease.