Meulengracht Disease - UGT1A1

Gilbert syndrome

Clinical Features

Gilbert syndrome is a benign form of chronic, non haemolytic hyperbilirubinemia. Unconjugated and total bilirubin levels are found to be continuously or temporarily elevated (environmental and external factors). The remaining laboratory values are within the normal range. The underlying cause of this genetically determined disposition is a defective synthesis of bilirubin-UDP-glucuronyl transferase to around 30% of normal control levels. Infants with Gilbert syndrome may have a greater increase in neonatal jaundice, but without other co-factors jaundice is comparable to other neonates. Kernicterus due to Gilbert syndrome has not been described.

Genetic Information

The Gilbert syndrome is an autosomal recessively inherited condition caused by the expansion of a dinucleotide repeat in the regulatory region (promotor) of the UGT1A1 (UDP-glucuronyl transferase) gene on chromosome 2 (2q37). In around 80% this repeat expansion (TA 7) is homozygous, i.e. present on both alleles. In around 20% of the individuals affected by Gilbert syndrome, only one allele carries the dinucleotide repeat expansion. The number of individuals clinically affected by Gilbert syndrome is exceeded by the number of individuals homozygous for the repeat expansion. Therefore, environmental factors such as nutritional habits (fat, alcohol intake or nicotine abuse) may modify the disease risk.

Prevalence

The prevalence of homozygous gene carriers is about 1 : 10 in our population; the prevalence of Gilbert syndrome is lower, with more males than females being affected.