Gilbert Syndrome is an inherited condition that is caused by certain gene mutations that are passed down through family generations.
What are the other Names for this Condition? (Also known as/Synonyms)
- Gilbert-Lereboullet Syndrome
- Gilbert–Meulengracht Syndrome
- Gilbert's Disease
What is Gilbert Syndrome? (Definition/Background Information)
- Gilbert Syndrome is an inherited condition that is caused by certain gene mutations that are passed down through family generations. Currently, there are no other risk factors associated with Gilbert Syndrome and it is inherited from one’s parents
- Gilbert Syndrome is caused, when the defective UGT1A1 gene that cannot properly produce a necessary protein in the body, is inherited in an autosomal recessive manner. Individuals with Gilbert Syndrome do not have the protein responsible for breakdown of bilirubin (a product of red blood cells)
- Gilbert Syndrome is typically mild and is characterized by the inability of the liver to process bilirubin. The main sign of Gilbert Syndrome is yellowing of the skin or eyes (jaundice) and feeling of tiredness. Jaundice in these individuals most usually occurs during stressful situations such as during illness, exercise, dehydration, or even during fasting
- Complications associated with Gilbert Syndrome include being unable to receive certain drugs, including chemotherapy drugs or drugs that treat HIV. Other than avoiding these medications, there are generally no known complications associated with Gilbert Syndrome
- Not all individuals with Gilbert Syndrome require treatment, especially if the signs and symptoms are mild. The body levels of bilirubin often change and if they increase enough, the condition may manifest as jaundice. However, this is self-resolving, and the levels of bilirubin automatically decrease on their own with no adverse effects after some time
- There is no known prevention of Gilbert Syndrome, since this disorder is passed down families. The episodes of high bilirubin levels in blood can be prevented, however, by preventing strenuous exercise, periods of fasting, or other stressful conditions
- Gilbert Syndrome has a good prognosis and individuals who have this disorder generally live a normal and healthy life
Who gets Gilbert Syndrome? (Age and Sex Distribution)
- Gilbert Syndrome is a congenital genetic disorder, but this condition is usually diagnosed in younger individuals typically after puberty or into adulthood (around or between 15-25 years)
- In terms of the sex distribution of Gilbert Syndrome, this condition affects more males than females. There is about a two-fold risk in males of developing the disorder compared to females (male-female ratio of 2:1)
- There is no race or ethnic group that is specific to the disorder. The geographical distribution of Gilbert Syndrome is generally uniform around the world
- The incidence of Gilbert Syndrome in the general population is around 1 in 15 to 1 in 30; meaning between 3-7% of all individuals may be affected
What are the Risk Factors for Gilbert Syndrome? (Predisposing Factors)
Gilbert Syndrome is an inherited genetic disorder, and hence, a family history of Gilbert Syndrome is the main risk factor.
- There are no environmental risk factors that increase one’s risk of developing Gilbert Syndrome
- Nevertheless, in individuals with the disorder, the following conditions are known to increase the episodes of high bilirubin in blood. These stressful conditions include
- Fasting or being without food for a long time duration
- Being ill
- Strenuous exercises
- Menstruation in girls
- Intake of alcohol
- During these stressful conditions, the amount of bilirubin in blood is increased, which increases the episodes associated with Gilbert Syndrome. Nevertheless, such events or episodes are typically mild
It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.
Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.
What are the Causes of Gilbert Syndrome? (Etiology)
Gilbert Syndrome is caused by the inheritance of an abnormal gene (the UGT1A1 gene). The disorder develops following inheritance of the gene from both the father and mother (both parents) in an autosomal recessive manner.
- The normal, healthy version of the gene codes for an enzyme (a protein) that is involved in breaking down bilirubin in liver. When this defective gene is inherited, the normal version of the enzyme cannot be produced in the body
- When old, worn out red blood cells are cleared from the body to be replaced by newer, healthier cells, bilirubin is produced by the liver and released into the bloodstream
- Bilirubin is normally broken down in the liver and cleared from the body through stool. But, individuals with Gilbert Syndrome do not have the protein responsible for breaking bilirubin down. Thus, bilirubin cannot be cleared from the bloodstream, as a result of which, their levels stay high in blood
Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).
There is no difference in geographical distribution of Gilbert Syndrome, though different regions of the world appear to have different gene mutations causing Gilbert Syndrome
- In Asia, the mutation is most prevalent in the coding sequence of the gene (or the region of the gene that codes for the protein)
- Whereas Caucasians appear to have a gene mutation that is most prevalent in the promoter region (or the region of the gene that regulates how often the protein is produced)
What are the Signs and Symptoms of Gilbert Syndrome?
The signs and symptoms of Gilbert Syndrome may include:
- The key symptom of Gilbert Syndrome is a slight yellowish tinge to the eye whites or to the skin. This yellow color is a result of the buildup of bilirubin (a yellowish breakdown product), which gets noticeably deposited in the skin and whites of the eyes
- While this is the only obvious indication of the disorder, there are certain situations that can increase the levels of bilirubin in the bloodstream in individuals with Gilbert Syndrome
Some of these conditions include falling sick (such as due to the common cold or the flu), long periods of low food intake (fasting), dehydration or strenuous exercising, not enough sleep, menstruation in girls and women, and any other condition causing stress to the body.
How is Gilbert Syndrome Diagnosed?
The diagnosis of Gilbert Syndrome may involve the following steps:
- Complete physical examination including medical and family history assessment, along with symptom check
- Blood tests: These blood tests are important to make sure that the symptoms are due to Gilbert Syndrome and not due to other liver-related conditions. These blood tests help ascertain the overall health status of the liver
- Complete blood count (CBC): Total blood counts are blood tests performed typically to diagnose a wide range of disorders. The test includes counting the numbers of specific types of cells in the bloodstream
- Liver function tests: Liver function tests are blood tests that are used to assess liver function and to see if the liver is inflamed or damaged
Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.
What are the possible Complications of Gilbert Syndrome?
The complications of Gilbert Syndrome are the result of the liver’s inability to process bilirubin, because of the presence of the defective enzyme.
- Individuals with Gilbert Syndrome cannot take certain medications, since the body lacks the enzyme associated with clearing these medications (or the detoxification of the drugs by liver is hampered). Such medications include irinotecan (a chemotherapy drug) and protease inhibitor drugs that are used to treat HIV
- Other possible complications of Gilbert Syndrome include the development of gallstones, which are hardened deposits of digestive fluids in the gallbladder
How is Gilbert Syndrome Treated?
In most cases, Gilbert Syndrome is generally mild and self-resolving. Hence, a treatment of the condition may not be required.
- In individuals who exhibit significant signs and symptoms, medication to decrease the level of bilirubin may be administered
- Levels of bilirubin fluctuate, though this is typically resolved in the body without other negative side effects
- Controlling or treating any underlying conditions that increase body exertion or stress may help resolve the signs and symptoms of Gilbert Syndrome earlier
How can Gilbert Syndrome be Prevented?
- Currently, there are no specific methods or guidelines to prevent Gilbert Syndrome, since it is a genetic condition
- Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
- If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
- Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Gilbert Syndrome
However, the side effects associated with Gilbert Syndrome may be prevented through the following measures:
- Through the management of stress and regularly having a healthy diet, which can help prevent the episodes of high bilirubin in the body
- Frequently going on a weight loss program may cause bilirubin levels to fluctuate greatly resulting in more severe signs and symptoms
- Avoiding stressful triggers such as alcohol consumption, heavy exercising, and dehydration
What is the Prognosis of Gilbert Syndrome? (Outcomes/Resolutions)
- Gilbert Syndrome is a genetic disorder that has a very good prognosis in a majority of cases. Individuals with the syndrome typically live a healthy life with a normal lifespan and with a normally-functioning liver
- Complications associated with Gilbert Syndrome can be prevented by avoiding stressful conditions, as well as by avoiding periods of fasting and ensuring a healthy diet high in calories
- High bilirubin levels in the bloodstream are usually self-resolving, unless they are associated with other medical conditions
Additional and Relevant Useful Information for Gilbert Syndrome:
- Several research studies have shown an inverse relationship between Gilbert Syndrome and cardiovascular diseases. Mild increases in bilirubin levels are seen to correlate with reduced risk for coronary heart diseases
- The liver function blood tests help assess liver functioning by measuring the levels of various substances produced by the liver
The following article link may help you understand the liver function blood tests:
What are some Useful Resources for Additional Information?
American Liver Foundation
39, Broadway, Suite 2700 New York, NY 10006
Phone: (212) 668-1000
Toll-Free: 1 (800) GO-LIVER
Fax: (212) 483-8179
References and Information Sources used for the Article:
Gilbert Syndrome (2012, February). In Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Retrieved February 26, 2016.
Gilbert Syndrome (2015). In National Organization for Rare Disorders. Retrieved February 26, 2016.
Gilbert's Syndrome in Children--Our Experience. (2007, May). Journal of Serbian Medical Society, 135(5-6), 317-320.
Helpful Peer-Reviewed Medical Articles:
Sugatani, J., Yamakawa, K., Yoshinari, K., Machida, T., Takagi, H., Mori, M., ... & Miwa, M. (2002). Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia. Biochemical and biophysical research communications, 292(2), 492-497.
Monaghan, G. M. R. R. B., Ryan, M., Hume, R., Burchell, B., & Seddon, R. (1996). Genetic variation in bilirubin UDP-glucuronosyltransferase gene promoter and Gilbert's syndrome. The Lancet, 347(9001), 578-581.
Bancroft, J. D., Kreamer, B., & Gourley, G. R. (1998). Gilbert syndrome accelerates development of neonatal jaundice. The Journal of pediatrics,132(4), 656-660.
del Giudice, E. M., Perrotta, S., Nobili, B., Specchia, C., d’Urzo, G., & Iolascon, A. (1999). Coinheritance of Gilbert syndrome increases the risk for developing gallstones in patients with hereditary spherocytosis. Blood, 94(7), 2259-2262.
Inoguchi, T., Sasaki, S., Kobayashi, K., Takayanagi, R., & Yamada, T. (2007). Relationship between Gilbert syndrome and prevalence of vascular complications in patients with diabetes. JaMa, 298(12), 1396-1400.
Owens, D., & Evans, J. (1975). Population studies on Gilbert's syndrome.Journal of medical genetics, 12(2), 152-156.
Rotger, M., Taffé, P., Bleiber, G., Günthard, H. F., Furrer, H., Vernazza, P., ... & Swiss HIV Cohort Study. (2005). Gilbert syndrome and the development of antiretroviral therapy–associated hyperbilirubinemia. The Journal of infectious diseases, 192(8), 1381-1386.
Boon, A. C., Hawkins, C. L., Bisht, K., Coombes, J. S., Bakrania, B., Wagner, K. H., & Bulmer, A. C. (2012). Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome. Free Radical Biology and Medicine, 52(10), 2120-2127.