Amol Bhalchandra Deore

Abstract

Crigler-Najjar Syndrome type 2 [CN-2] is an uncommon inherited disorder characterized by non-hemolytic unconjugated hyperbilirubinemia. It is caused by mutations in one of the five exons of the UGT1A1 gene which codes for the enzyme hepatic uridine diphosphate glucoronosyl transferase-1, required for the conjugation and further excretion of bilirubin from the body via bile. Affected people are usually asymptomatic apart from jaundice and investigations reveal isolated indirect hyperbilirubinemia. It can be conveniently diagnosed by evaluating the response to phenobarbital in terms of reduction in bilirubin levels. Genetic testing confirms the finding of Crigler-Najjar syndrome. At least 20 different mutations of UGT1A1 have been associated with CN-2; all encode a bilirubin-uridine diphosphate glucuronosyl transferase-1 with markedly reduced but detectable enzymatic activity. Bilirubin concentrations are typically lower in CN-2, and plasma bilirubin levels can be reduced to 3 to 5 mg/dL by phenobarbital. Although uncommon in CN-2, bilirubin encephalopathy has occurred at all ages, typically associated with factors that temporarily elevation the plasma bilirubin concentration above baseline e.g. stress, prolonged fasting, an intercurrent illness like influenza. For this reason, phenobarbital therapy is often recommended. CN-2 is infrequent, and only a few pregnancies with this condition have been reported. The objective of the case study is to report a rare case of maternal CN-2 in the pregnancy and to evaluate whether pregnancy is safe in patients with the disease. A 29 years old mother with CN-2 had given birth to a baby girl by spontaneous vaginal delivery without complications. The newborn had mild unconjugated hyperbilirubinemia which was further treated by phototherapy and early morning sunlight. It can be concluded that that pregnancy need not be contraindicated in CN-2. Keywords: Hyperbilirubinemia, Phototherapy, UGT1A1 gene, Jaundice, Glucuronidation.

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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. Keywords: Hyperbilirubinemia, Phenobarbitone, UGT1A1 gene, Bilirubin, Jaundice, Mutations

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