Crigler najjar syndrome: A systematic outline

Abstract

Crigler-Najjar Syndrome (CNS) is a rare genetic condition characterized by non-hemolytic unconjugated hyperbilirubinemia. It is caused by mutations in the UGT1A1 gene which codes for the enzyme uridine diphosphate glucoronosyl transferase-1, required for the conjugation and further elimination of bilirubin from the body. Affected individuals are usually asymptomatic apart from the jaundice and investigations reveal isolated indirect hyperbilirubinemia. It can be conveniently diagnosed by evaluating the response to phenobarbital in terms of decrease in bilirubin levels. Genetic testing of the UGT1A1 gene for mutations is the investigative clincher. The hallmark outcome of Crigler-Najjar syndrome is a determined yellowing of the skin, mucous membranes and the sclera of eye. There are two patterns of this disorder: Crigler-Najjar syndrome type I, characterized by a nearly complete lack of enzyme activity and severe symptoms; and Crigler-Najjar syndrome type II, characterized by inadequate enzyme activity and milder symptoms. Both forms are inherited as autosomal recessive characters and are caused by faults or mutations of the UGT1A1 gene. Treatment is engaged toward dropping the level of unconjugated bilirubin in the blood. Early treatment is vibrant in Crigler-Najjar syndrome type I to prevent the development of encephalopathy during the first few months of life. Because Crigler-Najjar syndrome type II is milder and responds to phenobarbital, treatment is different. The purpose of the current review article is to emphasize on causes, types, clinical symptoms, autosomal pattern, complications, management and future direction for treatment of Crigler-Najjar syndrome.

Bilirubin metabolism: delving into the cellular and molecular mechanisms to predict complications

“…There are two distinct kinds of Crigler-Najjar syndrome: type I, which is distinguished by a nearly complete absence of enzyme activity and the presence of noticeable symptoms; and type II, which is characterized by limited enzyme activity and less noticeable symptoms. Encephalopathy, which results in coloration in many basal ganglia regions including the globus pallidus, subthalamic nuclei, and cranial nerve nuclei, can be caused by both CNS types 1 and 2 [52]. Unconjugated hyperbilirubinemia is commonly caused by neonatal jaundice and Gilbert syndrome [53].…”

Maternal outcome of Crigler-Najjar syndrome type-2: Case report

“…Two of these inborn errors in metabolism [Crigler-Najjar syndromes 1 and 2] can be fatal while the third [Gilbert's syndrome] is less serious. 1,2 In CN-1, there is a complete absence of hepatic UDP-glucuronosyltransferase-1 activity, whereas patients with CN-2 have up to 10% of normal and patients with Gilbert's syndrome have 10 to 30% of normal, leading to bilirubin concentrations of 18 to 45, 6 to 25, and 1.5 to 4 mg/dL, respectively. Patients with CN-1 and CN-2 are either homozygotes or double heterozygotes for structural mutations within the coding region.…”