Gilbert’s syndrome
Overview
Gilbert syndrome is a relatively mild condition characterized by periods of elevated levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin, which has an orange-yellow tint, is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Gilbert syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia). In affected individuals, bilirubin levels fluctuate and very rarely increase to levels that cause jaundice, which is yellowing of the skin and whites of the eyes.
Symptoms
The lone sign of Gilbert's disease is that your skin and the whites of your eyes occasionally have a yellowish tinge (jaundice). This is caused by the slightly elevated levels of bilirubin in your blood. Some conditions and situations may increase bilirubin levels, and thereby jaundice, in people with Gilbert's syndrome. These include:
- Illness, such as a cold or the flu
- Fasting or eating a very low-calorie diet
- Dehydration
- Menstruation
- Stress
- Strenuous exercise
- Lack of sleep
The jaundice will go away when these conditions resolve.
Causes
Changes in the UGT1A1 gene cause Gilbert syndrome. This gene provides instructions for making the bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme, which is found primarily in liver cells and is necessary for the removal of bilirubin from the body.
The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. During this reaction, the enzyme transfers a compound called glucuronic acid to unconjugated bilirubin, converting it to conjugated bilirubin. Glucuronidation makes bilirubin dissolvable in water so that it can be removed from the body.
Gilbert syndrome occurs worldwide, but some mutations occur more often in particular populations. In many populations, the most common genetic change that causes Gilbert syndrome (known as UGT1A1*28) occurs in an area near the UGT1A1 gene called the promoter region, which controls the production of the bilirubin-UGT enzyme. This genetic change impairs enzyme production. However, this change is uncommon in Asian populations, and affected Asians often have a mutation that changes a single protein building block (amino acid) in the bilirubin-UGT enzyme. This type of mutation, known as a missense mutation, results in reduced enzyme function.
Gilbert syndrome can have different inheritance patterns. When the condition is caused by the UGT1A1*28 change in the promoter region of the UGT1A1 gene, it is inherited in an autosomal recessive pattern. When the condition is caused by a missense mutation in the UGT1A1 gene, it is inherited in an autosomal dominant pattern.
Prevention
Gilbert syndrome is an inherited genetic disorder. Getting the disorder isn't related to lifestyle habits or environment. The only way to theoretically prevent the condition is to keep parents from passing the abnormal gene that causes it on to their children. But more than half the people in the general population carry one copy of this abnormal gene, making it very common. If two people with this abnormal gene have a child, they may pass along the genetic defect that causes Gilbert syndrome — but not always.
Diagnosis
If you have jaundice, your doctor may suspect that you have Gilbert syndrome or perhaps another condition. Often, though, Gilbert is found purely by accident when you have blood tests for other health reasons. Although it's present from birth, Gilbert syndrome usually isn't diagnosed until puberty or later, when bilirubin production increases.