Glucuronyl transferase deficiency and mild hereditary spherocytosis: effect of splenectomy

In a 6-year-old girl an association of hereditary spherocytosis and a defect in hepatic bilirubin metabolism has been found. The patient suffered from mild compensated haemolytic anaemia and excessive hyperbilirubinaemia (maximum concentration 581 mumol/l), the serum activity of liver enzymes was slightly increased. Examination of the erythrocyte membrane proteins revealed a deficiency of the major membrane skeletal protein, spectrin (about 75% of normal) which is probably the basic genetic defect of hereditary spherocytosis. Examination of the patient's family revealed a recessive mode of inheritance. The concentration of bilirubin conjugates in the patient's serum was decreased due to a reduced UDP-glucuronyl transferase activity found in homogenates of liver tissue. Histological liver examination showed an intrahepatic cholestasis, which is a secondary and reversible alteration resulting from severe hyperbilirubinaemia. After splenectomy, normalization of the increased haemolysis and hepatic dysfunction was observed. The excessive hyperbilirubinaemia can be explained by the association of an increased bilirubin load due to haemolytic anaemia and the diminished hepatic conjugation of bilirubin.