Gilbert's syndrome
Encyclopedia
Gilbert's syndrome often shortened to GS, also called Gilbert-Meulengracht syndrome, is the most common hereditary cause of increased bilirubin
and is found in up to 5% of the population (though some gastroenterologists
maintain that it is closer to 10%). A major characteristic is jaundice
, caused by elevated levels of unconjugated bilirubin in the bloodstream (hyperbilirubinemia).
The cause of this hyperbilirubinemia is the reduced activity of the enzyme
glucuronyltransferase, which conjugates
bilirubin and some other lipophilic molecules. Conjugation renders the bilirubin water-soluble, after which it is excreted in bile
into the duodenum
.
stream but normally has no serious consequences. Mild jaundice
may appear under conditions of exertion, stress, fasting, and infections, but the condition is otherwise usually asymptomatic.
It has been reported that GS may contribute to an accelerated onset of neonatal jaundice, especially in the presence of increased hemolysis
due to diseases like G6PD deficiency. This situation can be especially dangerous if not quickly treated as the high bilirubin causes irreversible neurological disability in the form of kernicterus
.
's ability to detoxify certain drugs. For example, Gilbert's syndrome is associated with severe diarrhea and neutropenia
in patients who are treated with irinotecan
, which is metabolized by UGT1A1.
While paracetamol
(acetaminophen or brand names Panadol, Tylenol) is not metabolized by UGT1A1
, it is metabolized by one of the other enzymes also deficient in some people with GS. A subset of people with GS may have an increased risk of paracetamol toxicity.
Specifically, people with mildly elevated levels of bilirubin (1.1 mg/dl to 2.7 mg/dl) were at lower risk for CAD and at lower risk for future heart disease. These researchers went on to perform a meta-analysis
of data available up to 2002, and confirmed that the incidence of atherosclerotic disease
(hardening of the arteries) in subjects with GS had a close and inverse relationship to the serum bilirubin. This beneficial effect was attributed to bilirubin IXα which is recognised as a potent antioxidant, rather than confounding
factors such as high-density lipoprotein (HDL) levels.
This association was also seen in long-term data from the Framingham Heart Study
. Moderately elevated levels of bilirubin in people with GS and the (TA)7/(TA)7 genotype was associated with 1/3 the risk for both coronary heart disease and cardiovascular disease as compared to those with the (TA)6/(TA)6 genotype (i.e. a normal, non-mutated gene locus).
A detailed summary of pre-2008 findings between cardiovascular disease and elevated serum bilirubin concentrations also discussed the concept of intentional, artificial raising of bilirubin levels as a means of prevention of cardiovascular disease and other oxidative and inflammatory diseases.
effect, characterized by mild jaundice
due to increased unconjugated bilirubin
, that arises from several different genotypic
variants of the gene for the enzyme
responsible for changing bilirubin
to the conjugated form.
Gilbert's syndrome is characterized by a 70%-80% reduction, rather than more severe loss of activity, in the glucuronidation
activity of the enzyme, uridine-diphosphate-glucuronosyltransferase isoform 1A1
(UDP-glucuronosyltransferase 1A1, or UGT1A1). The UGT1A1
gene is located on human chromosome 2.
There are considerably in excess of 100 variants of the UGT1A1 gene, designated as UGT1A1*n (where n is the general chronological order of discovery), either of the gene itself or of its promoter region. The UGT1A1 gene is associated with a TATA box
promoter region ; this region most commonly contains the genetic sequence A(TA6)TAA; this variant accounts for about 50% of allele
s in many populations. There are however several allelic polymorphic variants
of this region, the most common adding another dinucleotide repeat
TA to the promoter region, so that it is thus referred to as A(TA7)TAA, being also called UGT1A1*28; this common variant accounts for about 40% of alleles in some populations, but is seen less often, approximately 3% of alleles, in southeast and east Asian people and Pacific Islanders.
In most populations, Gilbert's syndrome is most commonly associated with homozygous A(TA7)TAA alleles. In 94% of GS cases, two other glucoronyltransferase enzymes, UGT1A6
(rendered 50% inactive) and UGT1A7 (rendered 83% ineffective), are also affected.
However, Gilbert's syndrome can arise without TATA box promoter polymorphic mutations; in some populations, particularly healthy southeast and east Asians, Gilbert's syndrome is more often a consequence of heterozygote missense mutations (such as Gly71Arg also known as UGT1A1*6, Tyr486Asp also known as UGT1A1*7, Pro364Leu also known as UGT1A1*73) in the actual gene coding region, which may be associated with significantly higher bilirubin levels.
Because of its effects on drug and bilirubin breakdown and because of its genetic inheritance, Gilbert's syndrome can be classed as a minor inborn error of metabolism.
The level of total bilirubin is often further increased if the blood sample is taken after fasting
for two days, and a fast can therefore be useful diagnostically. A further conceptual step that is rarely necessary or appropriate is to give a low dose of phenobarbital
; the bilirubin will decrease substantially.
There are also tests that detect DNA mutations of UGT1A1 by polymerase chain reaction
or DNA fragment sequencing.
and co-workers in 1901. In German literature, it is commonly associated with Jens Einar Meulengracht.
Alternative, less common names for this disorder include:
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
and is found in up to 5% of the population (though some gastroenterologists
Gastroenterology
Gastroenterology is the branch of medicine whereby the digestive system and its disorders are studied. The name is a combination of three Ancient Greek words gaster , enteron , and logos...
maintain that it is closer to 10%). A major characteristic is jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, caused by elevated levels of unconjugated bilirubin in the bloodstream (hyperbilirubinemia).
The cause of this hyperbilirubinemia is the reduced activity of the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
glucuronyltransferase, which conjugates
Conjugated system
In chemistry, a conjugated system is a system of connected p-orbitals with delocalized electrons in compounds with alternating single and multiple bonds, which in general may lower the overall energy of the molecule and increase stability. Lone pairs, radicals or carbenium ions may be part of the...
bilirubin and some other lipophilic molecules. Conjugation renders the bilirubin water-soluble, after which it is excreted in bile
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...
into the duodenum
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
.
Jaundice
Gilbert's syndrome produces an elevated level of unconjugated bilirubin in the bloodBlood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
stream but normally has no serious consequences. Mild jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
may appear under conditions of exertion, stress, fasting, and infections, but the condition is otherwise usually asymptomatic.
It has been reported that GS may contribute to an accelerated onset of neonatal jaundice, especially in the presence of increased hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
due to diseases like G6PD deficiency. This situation can be especially dangerous if not quickly treated as the high bilirubin causes irreversible neurological disability in the form of kernicterus
Kernicterus
Kernicterus is damage to the brain centers of infants caused by increased levels of unconjugated bilirubin. This may be due to several underlying pathologic processes. Newborn babies are often polycythemic. When they break down the erythrocytes, one of the byproducts is bilirubin, which circulates...
.
Detoxification of certain drugs
The enzymes that are defective in GS (UGT1A1) are also responsible for some of the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
's ability to detoxify certain drugs. For example, Gilbert's syndrome is associated with severe diarrhea and neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
in patients who are treated with irinotecan
Irinotecan
Irinotecan is a drug used for the treatment of cancer.Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1. In chemical terms, it is a semisynthetic analogue of the natural alkaloid camptothecin....
, which is metabolized by UGT1A1.
While paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
(acetaminophen or brand names Panadol, Tylenol) is not metabolized by UGT1A1
UGT1A1
UDP-glucuronosyltransferase 1-1 also known as UGT-1A is an enzyme that in humans is encoded by the UGT1A1 gene.UGT-1A is a uridine diphosphate glucuronyltransferase , an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and...
, it is metabolized by one of the other enzymes also deficient in some people with GS. A subset of people with GS may have an increased risk of paracetamol toxicity.
Cardiovascular effects
Several analyses have found a significantly decreased risk of coronary artery disease (CAD) in individuals with GS.Specifically, people with mildly elevated levels of bilirubin (1.1 mg/dl to 2.7 mg/dl) were at lower risk for CAD and at lower risk for future heart disease. These researchers went on to perform a meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of data available up to 2002, and confirmed that the incidence of atherosclerotic disease
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
(hardening of the arteries) in subjects with GS had a close and inverse relationship to the serum bilirubin. This beneficial effect was attributed to bilirubin IXα which is recognised as a potent antioxidant, rather than confounding
Confounding
In statistics, a confounding variable is an extraneous variable in a statistical model that correlates with both the dependent variable and the independent variable...
factors such as high-density lipoprotein (HDL) levels.
This association was also seen in long-term data from the Framingham Heart Study
Framingham Heart Study
The Framingham Heart Study is a long-term, ongoing cardiovascular study on residents of the town of Framingham, Massachusetts. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of participants...
. Moderately elevated levels of bilirubin in people with GS and the (TA)7/(TA)7 genotype was associated with 1/3 the risk for both coronary heart disease and cardiovascular disease as compared to those with the (TA)6/(TA)6 genotype (i.e. a normal, non-mutated gene locus).
A detailed summary of pre-2008 findings between cardiovascular disease and elevated serum bilirubin concentrations also discussed the concept of intentional, artificial raising of bilirubin levels as a means of prevention of cardiovascular disease and other oxidative and inflammatory diseases.
Debated signs and diffuse symptoms
Diffuse symptoms, whether connected or not to GS, have been reported in a subset of those affected: feeling tired all the time (fatigue), difficulty maintaining concentration, loss of appetite, abdominal pain, loss of weight and others, but scientific studies found no clear pattern of adverse symptoms related to the elevated levels of unconjugated bilirubin in adults (see below). There is consequently debate about whether GS should be classified as a disease.Cause
Gilbert's syndrome is a phenotypicPhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
effect, characterized by mild jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
due to increased unconjugated bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
, that arises from several different genotypic
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
variants of the gene for the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
responsible for changing bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
to the conjugated form.
Gilbert's syndrome is characterized by a 70%-80% reduction, rather than more severe loss of activity, in the glucuronidation
Glucuronidation
Glucuronidation is the addition of glucuronic acid to a substrate. Glucuronidation is often involved in xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids...
activity of the enzyme, uridine-diphosphate-glucuronosyltransferase isoform 1A1
Glucuronosyltransferase
Uridine 5'-diphospho-glucuronosyltransferase is a glycosyltransferase that catalyzes addition of the glycosyl group from a UTP-sugar to a small hydrophobic molecule.This is glucuronidation reaction.Alternative names:...
(UDP-glucuronosyltransferase 1A1, or UGT1A1). The UGT1A1
UGT1A1
UDP-glucuronosyltransferase 1-1 also known as UGT-1A is an enzyme that in humans is encoded by the UGT1A1 gene.UGT-1A is a uridine diphosphate glucuronyltransferase , an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and...
gene is located on human chromosome 2.
There are considerably in excess of 100 variants of the UGT1A1 gene, designated as UGT1A1*n (where n is the general chronological order of discovery), either of the gene itself or of its promoter region. The UGT1A1 gene is associated with a TATA box
TATA box
The TATA box is a DNA sequence found in the promoter region of genes in archaea and eukaryotes; approximately 24% of human genes contain a TATA box within the core promoter....
promoter region ; this region most commonly contains the genetic sequence A(TA6)TAA; this variant accounts for about 50% of allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s in many populations. There are however several allelic polymorphic variants
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
of this region, the most common adding another dinucleotide repeat
Tandem repeat
Tandem repeats occur in DNA when a pattern of two or more nucleotides is repeated and the repetitions are directly adjacent to each other. -Example:An example would be:in which the sequence A-T-T-C-G is repeated three times.-Terminology:...
TA to the promoter region, so that it is thus referred to as A(TA7)TAA, being also called UGT1A1*28; this common variant accounts for about 40% of alleles in some populations, but is seen less often, approximately 3% of alleles, in southeast and east Asian people and Pacific Islanders.
In most populations, Gilbert's syndrome is most commonly associated with homozygous A(TA7)TAA alleles. In 94% of GS cases, two other glucoronyltransferase enzymes, UGT1A6
UGT1A6
UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the UGT1A6 gene.- Function :UDP-glucuronosyltransferase 1-6 is a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and...
(rendered 50% inactive) and UGT1A7 (rendered 83% ineffective), are also affected.
However, Gilbert's syndrome can arise without TATA box promoter polymorphic mutations; in some populations, particularly healthy southeast and east Asians, Gilbert's syndrome is more often a consequence of heterozygote missense mutations (such as Gly71Arg also known as UGT1A1*6, Tyr486Asp also known as UGT1A1*7, Pro364Leu also known as UGT1A1*73) in the actual gene coding region, which may be associated with significantly higher bilirubin levels.
Because of its effects on drug and bilirubin breakdown and because of its genetic inheritance, Gilbert's syndrome can be classed as a minor inborn error of metabolism.
Diagnosis
People with GS predominantly have elevated unconjugated bilirubin, while conjugated bilirubin is usually within the normal range and is less than 20% of the total. Levels of bilirubin in GS patients are reported to be from 20 μM to 90 μM (1.2 to 5.3 mg/dL) compared to the normal amount of < 20 μM. GS patients will have a ratio of unconjugated/conjugated (indirect/direct) bilirubin that is commensurately higher than those without GS.The level of total bilirubin is often further increased if the blood sample is taken after fasting
Fasting
Fasting is primarily the act of willingly abstaining from some or all food, drink, or both, for a period of time. An absolute fast is normally defined as abstinence from all food and liquid for a defined period, usually a single day , or several days. Other fasts may be only partially restrictive,...
for two days, and a fast can therefore be useful diagnostically. A further conceptual step that is rarely necessary or appropriate is to give a low dose of phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...
; the bilirubin will decrease substantially.
There are also tests that detect DNA mutations of UGT1A1 by polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
or DNA fragment sequencing.
Differential diagnosis
While this syndrome is considered harmless, it is clinically important because it may give rise to a concern about a blood or liver condition, which could be more dangerous. However, these conditions have additional indicators:- HemolysisHemolysisHemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
can be excluded by a full blood count, haptoglobin, lactate dehydrogenaseLactate dehydrogenaseLactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
levels and the absence of reticulocytosis (elevated reticulocytes in the blood would usually be observed in haemolytic anaemia). - Viral hepatitisViral hepatitisViral hepatitis is liver inflammation due to a viral infection. It may present in acute or chronic forms. The most common causes of viral hepatitis are the five unrelated hepatotropic viruses Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D, and Hepatitis E...
can be excluded by negative blood samples for antigens specific to the different hepatitis viruses. - CholestasisCholestasisIn medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system such as can occur from a gallstone or malignancy and metabolic types of...
can be excluded by the absence of lactate dehydrogenaseLactate dehydrogenaseLactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
, low levels of conjugated bilirubin and ultrasoundUltrasoundUltrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
scan of the bile ducts. - More severe types of glucoronyl transferase disorders like Crigler-Najjar syndromeCrigler-Najjar syndromeCrigler-Najjar Syndrome or CNS is a rare disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of blood. The disorder results in an inherited form of non-hemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in...
(types I and II). These are much more severe, with 0-10% UGT1A1 activity, with sufferers at risk of brain damage in infancy (type I) and teenage years (type II). - Dubin–Johnson syndrome and Rotor syndromeRotor syndromeRotor syndrome, also called Rotor type hyperbilirubinemia, is a rare, relatively benign autosomal recessive bilirubin disorder of unknown origin...
, which are rarer autosomal recessiveRecessiveIn genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
disorders that are characterized by an increase of conjugated bilirubin. - In GS, unless another disease of the liver is also present, the liver-enzymes ALATAlanine transaminaseAlanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
, ASATASATASAT can mean:* Anti-satellite weapon* The ASM-135 ASAT, an air-launched anti-satellite multi stage missile* aspartate transaminase, an enzyme in amino acid metabolism*Advanced Subsonic Aerial Target A UAV used by the British Army for AA training....
and albuminAlbuminAlbumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
are within normal ranges.
History
Gilbert's syndrome was first described by French gastroenterologist Augustin Nicolas GilbertAugustin Nicolas Gilbert
Augustin Nicolas Gilbert was a French physician who was born in the town of Buzancy, Ardennes. He received his doctorate from the University of Paris and became an interne at the Hôtel-Dieu de Paris. Later he was a professor of therapeutics and clinical medicine at Hôtel-Dieu...
and co-workers in 1901. In German literature, it is commonly associated with Jens Einar Meulengracht.
Alternative, less common names for this disorder include:
- Familial benign unconjugated hyperbilirubinaemia
- Constitutional liver dysfunction
- Familial non-hemolytic non-obstructive jaundice
- Icterus intermittens juvenilis
- Low-grade chronic hyperbilirubinemia
- Unconjugated benign bilirubinemia
Notable cases
- Napoleon I of FranceNapoleon I of FranceNapoleon Bonaparte was a French military and political leader during the latter stages of the French Revolution.As Napoleon I, he was Emperor of the French from 1804 to 1815...
- Arthur KornbergArthur KornbergArthur Kornberg was an American biochemist who won the Nobel Prize in Physiology or Medicine 1959 for his discovery of "the mechanisms in the biological synthesis of deoxyribonucleic acid " together with Dr. Severo Ochoa of New York University...
, Nobel laureate in Physiology or Medicine, 1959 - Nicky WireNicky WireNicholas Allen Jones, known as Nicky Wire, is the lyricist, bassist and occasional vocalist with the Welsh rock band Manic Street Preachers.-Early life:...
, Manic Street PreachersManic Street PreachersManic Street Preachers are a Welsh alternative rock band, formed in 1986. They are James Dean Bradfield, Nicky Wire, Richey Edwards and Sean Moore. The band are part of the Cardiff music scene, and were at their most prominent during the 1990s...
bassist. - Noel FieldingNoel FieldingNoel Fielding is a British artist, comedian and actor. He is known for his roles as Vince Noir in The Mighty Boosh, which he co-writes with comedy partner Julian Barratt, and as team captain on the music panel show Never Mind the Buzzcocks.-Stand-up comedy:Noel Fielding performed regularly as a...
(The Mighty Boosh) - James Padden (Irish Classical Pianist)
- Alexandr Dolgopolov (tennis player)
- A. J. BurnettA. J. BurnettAllan James "A. J." Burnett is a right-handed Major League Baseball starting pitcher for the New York Yankees. Previously, he played for the Florida Marlins and the Toronto Blue Jays...
(Starting Pitcher for the New York Yankees) - Hilary RobinsonHilary RobinsonHilary Robinson is a fictional character from the Australian Network Ten soap opera Neighbours, played by Anne Scott-Pendlebury. The character first appeared on-screen on 25 June 1987, returning in 1988, in a guest capacity and returned in a permanent role in 1989 and left the show in 1990. She...
(Children's Author)
External links
- GilbertsSyndrome.com – collection of information on Gilbert's Syndrome, including symptom survey
- Gilbert's Syndrome Fact Sheet at AllRefer Health
- Children's Liver Disease Foundation