Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

You are here: Molecular Genetics » Meulengracht (Gilbert) Syndrome

Meulengracht (Gilbert) Syndrome [E80.4]

OMIM numbers: 143500, 191740 (UGT1A1)

Dr. rer. nat. Christoph Marschall, Dipl.-Biol. Christine Schack,
Dipl.-Biol. Christina Sofeso

Scientific Background

The Meulengracht (Gilbert) syndrome causes a mild, chronically stable or intermittent, unconjugated hyperbilirubinemia without structural liver disease or hemolysis. It is the most common disease of the hepatic bilirubin metabolism and one of the most common causes of neonatal jaundice. The bilirubin concentration in the serum is approximately 1-6 mg/dl.

The Meulengracht (Gilbert) syndrome is caused by a congenital reduction of the synthesis of the bilirubin UDP glucuronosyltransferase to approximately 30% rest activity. Inheritance is autosomal recessive. The disorder is usually caused by a dinucleotide expansion [TA]6>[TA]7 (rs3064744) in the region of the TATA box of the UGT1A1 promoter. This causes a reduction of the transcription rate. The frequency of homozygous carriers of the [TA]7 polymorphism in the general population is 10-19%; the number of clinically manifest cases is estimated to be 2-12%. The phenotype is influenced by environmental factors as well as diet (fat, alcohol and nicotine consumption). The clinical diagnosis is established by prescribing a 400 calorie diet over a period of 24 h. Most homozygous carriers display a rise in bilirubin in the serum.

Heterozygosity for the [TA]7 allele has been associated with drug intolerance under treatment with irinotecan.