Gilbert syndrome

Gilbert syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Gilbert syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • constitutional liver dysfunction
  • familial nonhemolytic jaundice
  • Gilbert-Lereboullet syndrome
  • Gilbert's disease
  • hyperbilirubinemia I
  • Meulengracht's disease
  • unconjugated benign bilirubinemia

Disorder Subdivisions

  • None

General Discussion

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.

Symptoms

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.

Causes

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.

Affected Populations

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.

Standard Therapies

Diagnosis

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.



Treatment

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.

Investigational Therapies

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:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:



www.centerwatch.com



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

Email: jayanta.roy-chowdhury@einstein.yu.edu



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

Email: namita.roychowdhury@einstein.yu.edu

References

TEXTBOOKS

Rimoin D, Connor JM, Pyeritz RP, Korf BR. Eds. Emory and Rimoin's Principles and Practice of Medical Genetics. 4th ed. Churchill Livingstone. New York, NY; 2002:1803-1817.



Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:3083-3085.



Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:756-757.



JOURNAL ARTICLES

Rossi F, Francese M, Iodice RM, et al. Inherited disorders of bilirubin metabolism. Minerva Pediatr. 2005;57:53-63.



Monaghan G, McLellan A, McGeehan A, et al. Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn. J Pediatr. 1999;134:441-446.



Bosma PJ, Roy-Chowdhury J, Bakker C, et al. The genetic basis of the reduced expression of bilirubin UDP- glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med. 1995;3331171-1175.



Aono S, Adachi Y, Uyama E, et al. Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome. Lancet. 1995;345:958-959.



Koiwai O, Nishizawa M, Hasada K, et al. Gilbert's syndrome is caused by a heterozygous missense mutation in the gene for bilirubin UDP-glucuronosyltransferase. Hum Mole Genet. 1995;4:1183-1186.



INTERNET

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Gilbert Syndrome. Entry No: 143500. Last Edited January 12, 2012. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 15, 2012.



Mayo Clinic for Medical Education and Research. Gilbert's Syndrome. http://www.mayoclinic.com/health/gilberts-syndrome/DS00743. Updated August 2, 2011. Accessed February 15, 2012.



Mukherjee S. Gilbert Syndrome. Emedicine. http://emedicine.medscape.com/article/176822-overview .Updated June 8, 2011. Accessed February 15, 2012.

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



Children's Liver Disease Foundation

36 Great Charles Street

Birmingham, B3 3JY

United Kingdom

Tel: 01212123839

Fax: 01212124300

Email: info@childliverdisease.org

Internet: http://www.childliverdisease.org



Canadian Liver Foundation

3100 Steeles Avenue East Suite 801

Markham Ontario, L3R 8T3

Canada

Tel: 4164913353

Fax: 9057521540

Tel: 8005635483

Email: clf@liver.ca

Internet: http://www.liver.ca



British Liver Trust

2 Southampton Road

Ringwood, BH24 1HY

United Kingdom

Tel: 01425481320

Fax: 01425481335

Tel: 08006527330

Email: info@britishlivertrust.org.uk

Internet: http://www.britishlivertrust.org.uk



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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