Crigler - Najjar Syndrome Type 2: A Usual Presentation of a Rare Disease

Crigler - Najjar syndrome (CN) type 2 is caused by a partial defect in uridine diphosphate glucoronosyl transferase-1 (UGT1A1) activity. It is characterized by isolated clinical jaundice. A clinical diagnosis may be confirmed by a detailed history and a thorough clinical evaluation. It needs to be differentiated from Gilbert syndrome. The hallmark of this benign condition is abnormally high unconjugated hyperbilirubinemia and its prompt response to oral phenobarbital therapy with excellent prognosis. Needless investigations should be avoided. Enzyme and gene testing could increase financial constraints in benign disease. We report one such case.

Background: Non-hemolytic unconjugated hyperbilirubinemia is a disorder of bilirubin conjugation, characterized by a nearly complete lack of UGT1A1 enzyme activity resulting in severe, even life-threatening symptoms (Crigler - Najjar syndrome type 1, CN type 1); or by partial enzyme activity and milder symptoms (Crigler - Najjar type 2,CN type 2 or Gilbert’s syndrome, GS). It is caused by mutation in the gene UGT1A1 located on the long arm (q) of chromosome 2 (2q37) [1,2].

Crigler - Najjar syndrome is a rare disease with only few 100 cases described in the literature. Its incidence is estimated to be 1 in 1,000,000 births. The more common inherited unconjugated hyperbilirubinemia, GS, affects approximately 3–7% of adult population [1,2].

Disorders that causes unconjugated hyperbilirubinemia can be either result of excessive bilirubin production (hemolysis), or decreased clearance of bilirubin (hepatic or intestinal), or may be combinations of both [1,2]. Unconjugated bilirubin (bond to albumin, water-insoluble), is rapidly and selectively taken up by hepatocytes, converted, to bilirubin glucuronide, conjugates (water-soluble) and ultimately secreted into bile. In affected individuals, bilirubin conjugation is inhibited, resulting in abnormally high levels of unconjugated bilirubin in the blood (hyperbilirubinemia) [1-3].

Case presentation: In this report, we present a girl with recurrent episodes of non-hemolytic hyperbilirubinemia with high unconjugated bilirubin levels that decreased after phenobarbital treatment.