Meulengracht (Gilbert) syndrome (Meulengracht’s disease) leads to mild, chronically stable or intermittent, non-conjugated hyperbilirubinemia in the absence of structural liver disease or hemolysis. It is the most common disorder of the hepatic bilirubin metabolism and one of the most common causes of icterus neonatorum. Serum bilirubin concentration is about 1-6 mg/dl.
Meulengracht (Gilbert) syndrome is caused by a congenital, autosomal recessive restriction of the synthesis of bilirubin-UDP-glucuronyltransferase to about 30% residual activity. In most cases, the synthesis disorder is caused by a dinucleotide expansion in the TATA box region of the UGT1A1 gene (UGT1A1*28 allele, rs3064744), which reduces the transcription rate of the gene. The frequency of homozygous carriers of this promoter expansion is about 10-19% in the general population, with clinically manifested cases estimated at 2-12%. The phenotype is modulated by environmental factors and diet (fat, alcohol, and nicotine intake). In addition, carriers of UGT1A1 promoter expansion should expect intolerance symptoms during chemotherapy with irinotecan.
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