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 polypeptide 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 promoter 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 hemoglobin 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 often are 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 usually will 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
Badash, Michelle. "Gilbert Syndrome." Health Library. EBSCO, 18 Mar. 2013. Web. 23 July 2014.
Dugdale, David C. "Gilbert's Disease." MedlinePlus. US NLM, 13 May 2013. Web.
Fretzayas, A., et al. "Gilbert Syndrome." European Jour. of Pediatrics 171.1 (2012): 11–15. MEDLINE Complete. Web. 23 July 2014.
Genetics Home Reference. "Gilbert Syndrome." Genetics Home Reference. US NLM, 21 July 2014. Web. 23 July 2014.
Hirschfield, G. M., and G. Alexander. “Gilbert’s Syndrome: An Overview for Clinical Biochemists.” Annals of Clinical Biochemistry 43.5 (2006): 340–343. Print.
Worman, Howard J. The Liver Disorders and Hepatitis Sourcebook. Updated ed. New York: McGraw-Hill, 2006. Print.
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