S2389 Gilbert’s Syndrome Coexisting With Congenital Hemolytic Anemia Presenting as Marked Indirect Hyperbilirubinemia: A Diagnostic Dilemma

Abstract

INTRODUCTION: Gilbert’s syndrome (GS) is a common hereditary bilirubin metabolism disorder caused by reduction of uridine diphosphate-glucuronyl transferase 1A1 (UGT1A1) activity. It presents as mild chronic unconjugated hyperbilirubinemia in the absence of liver disease. Congenital hemolytic anemias commonly include hereditary spherocytosis (HS), Glucose 6-phosphate dehydrogenase (G6PD) deficiency, and other hemoglobinopathies that present with variable degrees of anemia, jaundice, and splenomegaly. We present a case of a 38-year-old female with co-existing GS and hemolytic anemia who presented with marked indirect hyperbilirubinemia. CASE DESCRIPTION/METHODS: A 38-year old African American female with a history of congenital hemolytic anemia (Hemoglobin C disease and G6PD Deficiency) complicated with splenomegaly and pigmented gallstones requiring cholecystectomy was referred to hepatology clinic for evaluation of marked elevation of indirect bilirubin. Labs revealed elevated total bilirubin, indirect bilirubin, anemia, and normal AST, ALT, Alkaline phosphatase (Figure 1). Total and indirect bilirubin levels were markedly elevated, more than expected in patients with hemolytic anemias. Therefore, a coexisting underlying bilirubin metabolism disorder was suspected. Genetic testing for Gilbert’s disease was ordered and revealed homozygous UGT1A1*28 mutation, confirming the diagnosis of Gilbert’s disease along with congenital hemolytic anemia. DISCUSSION: Gilbert’s syndrome (GS) is a hereditary disorder of bilirubin metabolism with a prevalence of 2-5 % in the general population. It is characterized by a mild, chronic, and fluctuating increase in indirect bilirubin levels in the absence of underlying liver disease. Congenital hemolytic anemia commonly includes hereditary spherocytosis, G6PD deficiency, and other hemoglobinopathies that presents with anemia, jaundice, and splenomegaly. Concomitant GS and hemolytic anemias is associated with higher levels of bilirubin and an increase in the tendency to develop pigmented gallstones. It possesses a diagnostic dilemma as many physicians attribute the hyperbilirubinemia to hemolysis and do not look for associated GS. Treatment is not always recommended, however patients who develop complications with pigmented gallstones (biliary obstruction, cholecystitis), cholecystectomy may be required. Splenectomy can also be considered in moderate to severe cases of hemolytic anemia. Small daily doses of phenobarbital have been used to reduce marked hyperbilirubinemia.Table 1.: Baseline laboratory characteristics.