Gilbert’s Syndrome is a genetic impairment in the glucuronidation pathway in the liver. This is one of the 4 components of the Phase 2 Detoxification System, also known as Hepatic Microsomal Enzymes. (Phase 1 is the Cytochrome P450 System, which is also subject to genetic variations.) Gilbert’s is the only recognised common inherited disorder of Phase 2; in fact 50% of people have genetic variations of the glutahione S-transferase enzymes, which can have major health consequences. See Environmental Illness page . Estimates of the prevalence of Gilbert’s range from 2% to >5% of the population. Although it has often been said to have no clinical significance, this does not explain why Gilbert’s “sufferers” are relatively common among our patients.
It is likely that such people are more vulnerable to adverse effects of physical, particularly hepatotoxic, stress. Indeed, stress tests have been used to confirm the diagnosis (calorie restriction to 400/day; intravenous nicotinic acid; oral Rifampicin); all these raise the bilirubin by competing for the role of substrate to the limited enzyme.
Those with Gilbert’s do seem to exhibit symptoms more often than is the norm after infections, toxic exposures and the like. It is probable that they are more vulnerable to, for instance, the potentially severe consequences of paracetamol toxicity.
Glucuronidation detoxifies all the following molecules