UGT1A1 Gene Mutation And Graves' Disease Complicated With Hepatic Failure:Case Report And Literature Review

UGT1A1 gene is a member of the glucuronyl transferase?UGT?gene family,located on chromosome 2q37,which is a very common SNP locus?rs4148323?.The polymorphism of UGT1A1*6 is shown as 211G>a,forming three genotypes:G/G,A/G and A/A,and the polymorphism of UGT1A1*6 is only found in Asian population.The frequency among the east Asian population is as high as 15.2%,and among the Chinese as high as 30%.UGT1A1,the product of UGT1A1 gene,plays akey role in the second phase of liver biotransformation,catalyzing the combination of glucuronic acid with endogenous substances,such as bilirubin and thyroxine to accelerate metabolism.The mutation of UGT1A1 gene causes complete or partial loss of its enzyme activity and leads to hereditary bilirubin metabolic disorders.Graves'disease with liver failure is rare in clinical practice,with complicated etiology,severe condition,difficult treatment,poor prognosis and high mortality.This paper made a case analysis and literature review on the correlation between UGT1A1 gene mutation and Graves' disease with liver failure.Objective Mutation of UGT1A1 gene can cause structural and functional abnormalities of glucuronic acid transferase,leading to insufficient bilirubin metabolism and leading to high unbound bilirubinemia.Detection of the polypeptide of UGT1A1 gene in Graves' disease patients with liver failure is conducive to accurate diagnosis,help clinical take reasonable treatment measures,effectively alleviate thyrotoxicosis and severe jaundice.It's very important to promp save the lives of patients,and conduct relevant genetic counseling.Methods:A case report a 20-year-old male patient to our center with hyperthyroidism and hyperbilirubinemia.He's identified with Graves disease combined with hepatic failure by clinical and laboratory biochemistry examination.DNA was extracted from peripheral blood leukocyte using column method.Primers were designed according to the encoding gene of UGT1A1 gene exon codes by Primer Premier 5.0 software,and UGT1A1 gene exon codes were detected by PCR technique.UGT1A1 gene polymorphism was found by comparing with reference sequences?nc₀00002.11 and nm₀00463.2?c.211G>A,p.?Gly71Arg?missense mutation.Clinical follow-up routes were designed and the patients' medical history was collected.Results:This patient was identified with Graves disease combined with hepatic failure after he's excluded from autoimmune hepatitis,alcoholic hepatitis and viral hepatitis by clinical data and biochemical test indexes.Further genetic testing revealed the polymorphism of UGT1A1 gene:c.211G>A,p.?Gly71Arg?,the 71st amino acid residue of the encoded protein was mutated from Gly to Arg and the autosomal genetic variation was missense mutation,which was diagnosed as crigler-najjar syndrome type 2 and Graves 's disease complicated with liver failure.Conclusion:We propose that Crigler-Najjar syndrome type 2 in the patient with Graves' disease combined with hepatic failure.The rapidly progressing thyroid hormone of Graves' disease reduces the activity of UGT1A1 enzyme and the mutation of UGT1A1 gene leads to complete or partial loss of the enzyme activity,leading to hereditary bilirubin metabolism disorder.Through the comprehensive treatment of artificial liver,hepatic enzyme inducer phenobarbital,immune modulator methylprednisolone and methimazole,thyroid toxicosis and severe jaundice were finally effectively alleviated to successfully patient's life.