Severe hyperbilirubinemia in a 10‐year‐old girl with a combined disorder of hereditary spherocytosis and Gilbert syndrome

Hereditary spherocytosis (HS) is the most common hemolytic anemia and is characterized by spherical, osmotically fragile erythrocytes that are selectively trapped by the spleen.Gilbert syndrome, which is characterized by mild and chronic unconjugated hyperbilirubinemia with chronic or intermittent jaundice in the absence of liver and hemolytic disease, is the most common inherited metabolic liver disorder, occurring in 3 -7% of the population.1,2 In the present report we describe severe hyperbilirubinemia and persistent bilirubinemia after splenectomy in a young girl with a combined disorder of hereditary spherocytosis and Gilbert syndrome. Case ReportA 10-year-old girl was admitted to Department of Pediatrics, Dokkyo University Hospital because of elevated serum bilirubin (Bil) with abnormal liver function.She was born to consanguineous parents after a full-term uneventful delivery.In the neonatal period she received phototherapy for 5 days because of hyperbilirubinemia.At 3 years of age she was admitted to Department of Pediatrics, Dokkyo University Hospital because anemia was noted by her local physician.We made a diagnosis of HS based on clinical features including chemical and hematologic fi ndings (reticulocytosis, spherocytes on blood smear, increased red cell osmotic fragility and normoblastic hyperplasia in bone marrow).However, there were no other family members with hematological abnormalities.Thereafter she persistently demonstrated mild jaundice but not anemia.Seven days before the current admission she had complained of nausea and vomiting with increased levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT).In the absence of improvement, she was admitted.Physical examination showed severe jaundice and hepatosplenomegaly, although her general condition was not considered severe.Laboratory data were as follows: Total (T) Bil 32.5 mg/dL, direct (D) Bil 18.2 mg/dL, indirect (In) Bil 14.3 mg/ dL, AST 164 U/L (normal 10 -34 U/L), ALT 433 U/L (normal 10 -30 U/L), alkaline phosphatase (ALP) 690 U/L (normal 160 -260 U/L), lactate dehydrogenase (LD) 456 U/L (normal 176 -353 U/L), ␥ -GTP 81 U/L (normal 8 -50 U/L), total bile acid 104.4 mol/L (normal <10 U/L) and C-reactive protein 0.8 mg/L (normal 10 -34 U/L).Peripheral blood tests were as follows: hemoglobin (Hb) 12.8 g/dL, hematocrit (Ht) 35.3%, red blood cells (RBC) 405 × 4 / L, platelet 27.0 × 10 4 / L, white blood cells (WBC) 8200/ L and reticulocyte 12.6%.Jaundice progressively worsened after admission (T.Bil 45.8 mg/dL, D.Bil 30.9 mg/dL).Ultrasonic tomography of the abdomen demonstrated cholelithiasis.A drain was surgically inserted into the gallbladder to relieve severe jaundice but this treatment was not fully effective, although temporary improvement was achieved.Various drugs were also administered but there was no response.However, 60 days after admission, spontaneous improvement was observed (T.Bil 4.7 mg/dL and D.Bil 3.6 mg/dL) and she was followed as an outpatient.After 1 year she underwent splenectomy, the reticulocyte count decreased to one-tenth of that before surgery and the serum haptoglobin normalized.However, serum bilirubin was persistently positive in a range between 1 and 3 mg/dL and improvement in the level of serum bilirubin following splenectomy was not clear.Therefore, we suspected a somatic hyperbilirubinemia, in particular, Gilbert syndrome and carried out further examination.