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NORD is very grateful to Namita Roy-Chowdhury, PhD, and Jayanta Roy-Chowdhury, MD, Professors of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Liver Research Center, for assistance in the preparation of this report.
Gilbert syndrome is a mild genetic liver disorder in which the body cannot properly process bilirubin, a yellowish waste product that is formed when old or worn out red blood cells are broken down (hemolysis). Individuals with Gilbert syndrome have elevated levels of bilirubin (hyperbilirubinemia), because they have a reduced level of a specific liver enzyme required for elimination of bilirubin. Most affected individuals have no symptoms (asymptomatic) or may only exhibit mild yellowing of the skin, mucous membranes, and whites of the eyes (jaundice). Jaundice may not be apparent until adolescence. Bilirubin levels may increase following stress, exertion, dehydration alcohol consumption, fasting, and/or infection. In some individuals, jaundice may only be apparent when triggered by one of these conditions. Gilbert syndrome is inherited as an autosomal recessive trait.
Although Gilbert syndrome may become apparent shortly after birth, it may not be recognized for many years. Episodes of mild jaundice may appear in young adults and is more common in males than females. Frequently, episodes of jaundice are overlooked. Gilbert syndrome is associated with fluctuating levels of bilirubin in the blood (hyperbilirubinemia). Bilirubin levels may increase with stress, strain, dehydration, fasting, infection or exposure to cold. In many individuals, jaundice is only evident when one of these triggers raises the bilirubin levels.
Some affected individuals have reported vague, unspecific symptoms including fatigue, weakness and gastrointestinal symptoms such as nausea, abdominal discomfort, and diarrhea. Researchers do not believe that these symptoms are related to excess bilirubin in the blood and may occur coincidentally or due to other reasons such as anxiety over the diagnosis.
Gilbert syndrome is inherited as an autosomal recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
Researchers have determined that Gilbert syndrome is caused by mutations to the UGT1A1 gene located on the long arm (q) of chromosome 2 (2q37). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 2q37" refers to band 37 on the long arm of chromosome 2. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
The UGT1A1 gene contains instructions for creating (encoding) a liver enzyme known as uridine disphosphate-glucuronosyltransferase-1A1 (UGT1A1). This enzyme is required for the conversion (conjugation) and subsequent excretion of bilirubin from the body.
Mild jaundice associated with Gilbert syndrome occurs due to reduced amounts of this enzyme, which results in the accumulation of unconjugated bilirubin in the body. Bilirubin is an orange-yellow bile pigment that is mainly a byproduct of the natural breakdown (degeneration) of red blood cells (hemolysis). Bilirubin circulates in the liquid portion of the blood (plasma) bound to a protein called albumin; this is called unconjugated bilirubin, which does not dissolve in water (water-insoluble). Normally, this unconjugated bilirubin is taken up by the liver cells and, with the help of the UGT1A1 enzyme, is converted to form water-soluble bilirubin glucuronides (conjugated bilirubin), which are then excreted in the bile. The bile is stored in the gall bladder and, when called upon, passes into the common bile duct and then into the upper portion of the small intestine (duodenum) and aids in digestion. Most bilirubin is eliminated from the body in the feces.
Individuals with Gilbert syndrome retain approximately one third of the normal UGT1A1 enzyme activity and are able to conjugate enough bilirubin to prevent symptoms from developing. However, in some cases, especially when an affected individual is fasting, dehydrated or not feeling well, mild jaundice may develop.
Gilbert syndrome is diagnosed more often in males than females. The disorder affects approximately 3-7 percent of individuals in the general population. Gilbert syndrome affects individuals of all races. It is present at birth, but may remain undiagnosed until the late teens or early twenties. Gilbert syndrome was first described in the medical literature in 1901.
Symptoms of the following disorders can be similar to those of Gilbert syndrome. Comparisons may be useful for a differential diagnosis.
Crigler-Najjar syndrome is a rare genetic disorder characterized by elevated levels of bilirubin in the blood (hyperbilirubinemia). Bilirubin is a yellow waste product that is formed when old or worn out red blood cells are broken down (hemolysis). Individuals with Crigler-Najjar syndrome develop hyperbilirubinemia in the absence of excessive hemolysis. The elevated bilirubin levels occur because affected individuals lack a specific liver enzyme required for conversion (conjugation) and subsequent excretion of bilirubin. The hallmark finding of Crigler-Najjar syndrome is persistent yellowing of the skin, mucous membranes and whites of the eyes (jaundice). There are two forms of this disorder: Crigler-Najjar syndrome type I, characterized by a nearly complete lack of UGT1A1 enzyme activity and severe symptoms; and Crigler-Najjar syndrome type II, characterized by partial enzyme activity and milder symptoms. Crigler-Najjar syndrome is inherited as an autosomal recessive trait. In both types of Crigler-Najjar syndrome, jaundice occurs continuously and is more intense than that in Gilbert syndrome (For more information on Crigler-Najjar syndrome, choose"Crigler-Najjar" as your search term in the Rare Disease Database.)
Rotor syndrome is an extremely rare inherited metabolic disorder characterized by the presence of excessive bilirubin in the blood (hyperbilirubinemia). The hyperbilirubinemia is caused by impaired storage of bilirubin in the liver. In most cases, affected individuals exhibit no symptoms of this disorder (asymptomatic). In some cases, persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice) is present. Unlike Crigler-Najjar syndromes or Gilbert syndrome, affected individuals have high levels of conjugated bilirubin. Rotor syndrome is thought to be inherited as an autosomal recessive trait.
Dubin-Johnson syndrome is a rare genetic liver disorder characterized by elevated levels of bilirubin in blood (hyperbilirubinemia). Persistent yellowing of the skin, mucous membranes and whites of the eyes (jaundice) is usually the only symptom in most cases. Dubin-Johnson syndrome is usually diagnosed after puberty. In rare cases, enlargement of the liver or spleen may occur (hepatomegaly). Like Rotor syndrome, and unlike Crigler-Najjar syndromes or Gilbert syndrome, high levels of conjugated bilirubin characterizes this disorder. Dubin-Johnson syndrome is inherited as an autosomal recessive disorder. (For more information, choose "Dubin Johnson" as your search term in the Rare Disease Database).
A diagnosis of Gilbert syndrome is often made when blood, drawn for routine health check up or another illness, such as an infection, detects mildly elevated bilirubin levels. Because the levels of bilirubin fluctuate, blood tests may not always show elevated bilirubin. Individuals are determined to have Gilbert syndrome by the presence of hyperbilirubinemia in the absence of hemolysis (premature breakdown of red blood cells) or structural liver damage.
In most cases, Gilbert syndrome does not cause symptoms and no treatment is necessary. Mild jaundice may occur, but does not cause any problems. Gilbert syndrome is considered a mild, harmless (benign) condition and is associated with normal life expectancy. Some medicines, such as the cancer therapy drug, irinotecan, may cause diarrhea, when administered in subjects with Gilbert syndrome.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, contact:
Contacts for additional information about Gilbert syndrome:
Jayanta Roy-Chowdhury, MD
Professor of Medicine and Molecular Genetics
Albert Einstein College of Medicine
Liver Research Center
Bronx, NY 10461
Tel: (718) 430-2265
Namita Roy-Chowdhury, PhD
Professor of Medicine and Molecular Genetics
Albert Einstein College of Medicine
Liver Research Center
Bronx, NY 10461
Tel: (718) 430-2254
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Report last updated: 2012/03/12 00:00:00 GMT+0