Coinheritance of Gilbert syndrome increases the risk for developing gallstones in patients with hereditary spherocytosis

The precocious formation of bilirubinate gallstones is the most common comp lication of hereditary spherocytosis (HS), and the prevention of this probl em represents a major impetus for splenectomy in many patients with compens ated hemolysis, Because Gilbert syndrome has been considered a risk factor for gallstone formation, there are reasons for postulating that the associa tion of this common inherited disorder of hepatic bilirubin metabolism with HS could increase cholelithiasis. To test this hypothesis, 103 children wi th mild to moderate HS who, from age 1, have undergone a liver and biliary tree ultrasonography every year, were retrospectively examined. The 2-bp (T A) insertion within the promoter of the uridine diphosphate-glucuronosyltra nsferase gene (UGT1A1), associated with Gilbert syndrome, was screened. The risk of developing gallstones was statistically different among the 3 grou ps of patients: homozygotes for the normal UGT1A1 allele, heterozygotes, an d homozygotes for the allele with the TA insertion. Fitting a Cox regressio n model, in fact, a statistically significant hazard ratio of 2.19 (95% con fidence interval: 1.31 to 3.66) was estimated from one to the next of these genetic classes. The individual proneness to form gallstones from TA inser tion in the TATA-box of the UGT1A1 promoter should be considered during the follow-up of patients with HS. Although patients with HS were the only one s studied, extrapolating these data to patients who have different forms of inherited (eg, thalassemia, intraerythrocytic enzymatic deficiency) or acq uired (eg, autoimmune hemolytic anemia, hemolysis from mechanical heart val ve replacement) chronic hemolysis can be warranted. (C) 1999 by The America n Society of Hematology.