HEREDITARY UNCONJUGATED HYPERBILIRUBINEMIA (COMBINATION OF CRIGLER-NAJJAR SYNDROME TYPE II AND GILBERT'S SYNDROME)

Abstract

Background. Enzymopathic jaundices are manifested by intermittent hyperbilirubinemia, no changes in the structure of the liver, no hemolysis, Rh-conflict as well as cholestasis being noted. These jaundices include Crigler-Najjar syndrome type I, Crigler-Najjar syndrome type II and Gilbert's syndrome. They are characterized by an autosomal recessive inheritance due to the presence of mutations and polymorphisms in uridine 5'-diphosphate-glucuronosyltransferase gene (UGT1A1) leading to a decrease of the enzyme activity or to its complete loss. Objective. To demonstrate the peculiarities of diagnosis and treatment of a rare case of hereditary unconjugated hyperbilirubinemia - a combination of Crigler-Najjar syndrome type II and Gilbert's syndrome. Material and methods. Clinical observation of a patient G. aged 19, who was examined and treated at the Department of gastroenterology of a multidisciplinary hospital in Moscow in January 2021. Results. The patient G. has had icteric sclerae and skin since birth; he occasionally suffers from easy fatigability and general malaise. Physical examination revealed no changes (except for icteric discoloration). An increase in unconjugated bilirubin up to 270 μmol/L (median - 170 μmol/L) was detected. The molecular genetic study of UGT1A1 gene identified mutations in exon 4 Val378Asp (2002) and Arg108Cys as well as polymorphism 6/7TA in the promoter region, confirming the diagnosis of autosomal recessive inherited disease – a combination of Crigler Najjar syndrome type II and Gilbert's syndrome (heterozygous state), complicated by the development of hepatic encephalopathy stage 2. There was noted a significant decrease in unconjugated bilirubin up to 170.5 μmol/L, as well as improvement in general condition – reduced fatigue and weakness during the treatment with microsomal enzyme inducer (phenobarbital) and hyperammonemia corrector (ornithine aspartate). Conclusions. The use of molecular genetic analysis allows tailoring strategies for patient-specific disease diagnostics, treatment and prevention. The preservation of quality of life within satisfactory level is achieved through elimination of adverse effects provoking the development of this syndrome and through control of risk factors.