Crigler-Najjar Syndrome Type 2

Abstract

Crigler-Najjar syndrome is a rare disorder of bilirubin metabolism with two distinct forms: type 1 and type 2. We report three patients with Crigler-Najjar syndrome type 2 (CN-2). All patients had serum bilirubin values higher than 171 μmol/L and deep yellow skin color. The results of other liver function tests, glucose-6-phosphate dehydrogenase activity and hematology tests were normal, and immunologic tests for hepatitis A, B and C were negative, although one patient had slightly elevated alanine aminotransferase level (45 IU/L). Polymerase chain reaction and sequence analysis of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene revealed a novel homozygous T > A mutation at nucleotide 479 in exon 1 (Val160Glu) of patient 1, a novel homozygous A >G mutation at nucleotide 610 in exon 1 (Met204Val) of patient 2, and a homozygous T >G variation at nucleotide 1456 in exon 5 (Tyr486Asp) plus a heterozygous G > A variation at nucleotide 211 in exon 1 (Gly71 Arg/normal) of patient 3. Two of these mutations were novel and variations identified within the coding region of the UGT1A1 gene were considered the cause of CN-2 in all three patients.

Keywords

• Crigler-Najjar syndrome
• glucuronosyltransferase
• novel mutation