Gilbert's syndrome
Gilbert's syndrome is a common, benign genetic liver disorder characterized by elevated levels of bilirubin in the bloodstream, which can lead to mild jaundice. It affects approximately 3 to 7 percent of the U.S. population and can manifest during adolescence or early adulthood. The condition is frequently inherited as an autosomal dominant trait, meaning that a family history increases the likelihood of developing the syndrome. Symptoms are often minimal or absent, but some individuals may experience jaundice, abdominal pain, fatigue, and dark urine.
The underlying cause of Gilbert's syndrome is reduced activity of the enzyme bilirubin glucuronosyltransferase, linked to a mutation in the UGT1A10 gene. Diagnosis typically involves a medical history review, physical examination, and blood tests to exclude other liver diseases. Importantly, Gilbert's syndrome does not require treatment, as symptoms usually resolve on their own. However, individuals may manage symptoms by avoiding fasting, dehydration, and stress. Understanding this condition can help demystify experiences of jaundice and promote awareness about genetic liver disorders.
Gilbert's syndrome
ALSO KNOWN AS: Gilbert syndrome; Gilbert's disease; hyperbilirubinemia
DEFINITION Gilbert’s syndrome is a common, benign genetic liver disorder. It causes levels of bilirubin to rise above normal levels. Bilirubin is a yellow chemical by-product of hemoglobin (the red pigment in blood cells) and is usually excreted by the liver as bile.
According to the American Liver Foundation in 2023, Gilbert’s syndrome is found in 3 to 7 percent of the US population. The condition affects individuals of all races. This condition usually manifests during the teen years or in adulthood (ages twenty to thirty).
Risk Factors
Individuals who have family members with Gilbert’s syndrome (autosomal dominant trait) are at risk for the disorder. People who have the disorder have a 50 percent chance of passing it on to each of their children. Males are also at an increased risk of developing the syndrome.
Etiology and Genetics
Patients with Gilbert’s syndrome have reduced activity of an enzyme known as bilirubin glucuronosyltransferase. This is a complex enzyme composed of several polypeptides, and the molecular defect is in UGT1A10 (also known as UGT1J), the gene that encodes the A10 of the UDP glucuronosyltransferase 1 family (formerly known as the UDP glycosyltransferase 1 family). This gene is found on the long arm of chromosome 2 at position 2q37. Molecular genetics studies have revealed the interesting fact that the mutation is not within the coding region of the gene itself but rather in a controlling element called the region. A two-base-pair repeat (insertion) in the mutated promoter causes drastically reduced levels of the protein to be synthesized.
Bilirubin is always present in small amounts in the bloodstream, since it is a waste product produced by the breakdown of in old red blood cells. In healthy individuals, the bilirubin is broken down further in the liver and excreted. This process is greatly slowed in individuals with Gilbert’s syndrome, so bilirubin accumulates in the blood and may cause yellowing of the skin or eyes.
In most cases, Gilbert’s syndrome is inherited as an autosomal recessive disorder, meaning that both copies of the gene must be deficient in order for the individual to show the trait. Typically, an affected child is born to two unaffected parents, both of whom are carriers of the recessive mutant allele. The probable outcomes for children whose parents are both carriers are 75 percent unaffected and 25 percent affected. If one parent has Gilbert’s syndrome and the other is a carrier, there is a 50 percent probability that each child will be affected. In some cases, however, carrier individuals will show some features of the syndrome even though only one of their two copies of the gene is mutant. Other studies have noted that, for unexplained reasons, some people who have two mutated copies of the gene do not develop Gilbert’s syndrome.
Symptoms
There are often no symptoms of Gilbert’s syndrome. However, people who do have symptoms may experience jaundice (yellowing) of the whites of the eyes, jaundice of the skin, abdominal pain, loss of appetite, fatigue and weakness, and darkening of the urine.
Screening and Diagnosis
The doctor will ask a patient about his or her symptoms and medical history and will perform a physical exam. Tests may include a complete blood count (CBC) and liver function tests. Blood tests are also done to rule out more serious liver diseases, such as hepatitis. Sometimes, a liver biopsy may also need to be done to rule out other liver diseases.
Treatment and Therapy
No treatment is necessary for Gilbert’s syndrome. Symptoms will usually disappear on their own.
Prevention and Outcomes
There is no way to prevent Gilbert’s syndrome. However, patients may prevent symptoms if they avoid skipping meals or fasting. Individuals should also avoid dehydration (too little fluid in the body), vigorous exercise, repeated bouts of vomiting, and stress or trauma.
Bibliography
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