Gilbert's Disease
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Gilbert syndrome (GS) is a syndrome in which the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
of affected individuals processes
bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
more slowly than the majority resulting in higher levels in the blood. Many people never have symptoms. Occasionally
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
(a yellowing of the skin or whites of the eyes) may occur. Gilbert syndrome is due to a genetic variant in the ''UGT1A1'' gene which results in decreased activity of the bilirubin uridine diphosphate glucuronosyltransferase enzyme. It is typically inherited in an
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
pattern and occasionally in an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
pattern depending on the type of variant. Episodes of jaundice may be triggered by stress such as exercise,
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...
, or not eating. Diagnosis is based on elevated levels of
unconjugated bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
in the blood without signs of
liver problems Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...
or red blood cell breakdown. Typically no treatment is needed.
Phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ...
aids in the conjugation of bilirubin and can be prescribed if jaundice becomes significant. Gilbert syndrome is associated with decreased cardiovascular health risks but increased risks of some cancers and gallstones. Gilbert syndrome affects about 5% of people in the United States. Males are more often diagnosed than females. It is often not noticed until late childhood to early adulthood. The condition was first described in 1901 by
Augustin Nicolas Gilbert Augustin Nicolas Gilbert (; 15 February 1858 – 4 March 1927) was a French physician. He was born in the town of Buzancy, Ardennes, and died in Paris. He received his doctorate from the University of Paris and became an intern at the Hôtel-Die ...
.


Signs and symptoms


Jaundice

Gilbert syndrome produces an elevated level of unconjugated bilirubin in the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
stream, but normally has no consequences. Mild
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
may appear under conditions of exertion, stress, fasting, and infections, but the condition is otherwise usually asymptomatic. Severe cases are seen by yellowing of the skin tone and yellowing of the conjunctiva in the eye. Gilbert syndrome has been reported to contribute to an accelerated onset of
neonatal jaundice Neonatal jaundice is a yellowish discoloration of the white part of the eyes and skin in a newborn baby due to high bilirubin levels. Other symptoms may include excess sleepiness or poor feeding. Complications may include seizures, cerebral ...
. The syndrome cannot cause severe indirect hyperbilirubinemia in neonates by itself, but it may have a summative effect on rising bilirubin when combined with other factors, for example in the presence of increased red blood cell destruction due to diseases such as
G6PD deficiency Glucose-6-phosphate dehydrogenase deficiency (G6PDD), also known as favism, is the most common enzyme deficiency anemia worldwide. It is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are ...
. This situation can be especially dangerous if not quickly treated, as the high serum bilirubin can cause irreversible neurological disability in the form of
kernicterus Kernicterus is a bilirubin-induced brain dysfunction. The term was coined in 1904 by Christian Georg Schmorl. Bilirubin is a naturally occurring substance in the body of humans and many other animals, but it is neurotoxic when its concentration ...
.


Effects on drug metabolism and drug interactions

The enzymes that are defective in GS – UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) – are also responsible for some of the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
's ability to detoxify certain drugs. For example, Gilbert syndrome is associated with severe diarrhea and
neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...
in patients who are treated with
irinotecan Irinotecan, sold under the brand name Camptosar among others, is an anti-cancer medication used to treat colon cancer and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is ...
, which is metabolized by UGT1A1. While
paracetamol Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...
(acetaminophen) 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. Another drug that has increased adverse side-effects in individuals with Gilbert Syndrome is atazanavir.Strassburg, C. P. (2008). Pharmacogenetics of gilbert's syndrome. ''Pharmacogenomics, 9''(6), 703-15. doi:https://doi.org/10.2217/14622416.9.6.703 Atazanavir is a protease inhibitor for the treatment of HIV. Atazanavir can lead to jaundice in individuals with Gilbert Syndrome because it further inhibits the UGT enzymes that are already exhibit decreased activity in Gilbert Syndome.


Cardiovascular effects

The mild increase in unconjugated bilirubin due to Gilbert syndrome is closely related to the reduction in the prevalence of chronic diseases, especially cardiovascular disease and type 2 diabetes, related risk factors, and all-cause mortality. Observational studies emphasize that the antioxidant effects of unconjugated bilirubin may bring survival benefits to patients. Several analyses have found a significantly decreased risk of
coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
(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 is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...
of data available up to 2002, and confirmed 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 recognized as a potent antioxidant, rather than
confounding In causal inference, a confounder is a variable that influences both the dependent variable and independent variable, causing a spurious association. Confounding is a causal concept, and as such, cannot be described in terms of correlatio ...
factors such as
high-density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...
levels. This association was also seen in long-term data from the
Framingham Heart Study The Framingham Heart Study is a long-term, ongoing cardiovascular cohort study of residents of the city of Framingham, Massachusetts. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of partic ...
. Moderately elevated levels of bilirubin in people with GS and the (TA)7/(TA)7 genotype were associated with one-third 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, nonmutated gene locus). Platelet counts and MPV (mean platelet volume) are decreased in patients with Gilbert's syndrome. The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilbert's syndrome patients may have an effect on the slowing down of the
atherosclerotic Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by elev ...
process.


Other symptoms and links to disease

Symptoms, whether connected or not to GS, have been reported in a subset of those affected:
fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...
(feeling tired all the time), difficulty maintaining concentration, unusual patterns of
anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...
, loss of
appetite Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to reg ...
,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...
, abdominal pain, loss of weight, itching (with no rash), and others,GilbertsSyndrome.com
such as humor change or depression. But scientific studies found no clear pattern of adverse symptoms related to the elevated levels of unconjugated bilirubin in adults. However, other substances glucuronidized by the affected enzymes in those with Gilbert's syndrome could theoretically, at their toxic levels, cause these symptoms. Consequently, debate exists about whether GS should be classified as a disease. Gilbert syndrome has been linked to an increased risk of
gallstone A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of ...
s,
schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
, breast cancer, and colorectal cancer. The theorized mechanism for the increased risk of breast cancer is elevated estrogen from its decreased metabolism by
UDP-glucuronosyltransferase Uridine 5'-diphospho-glucuronosyltransferase ( UDP-glucuronosyltransferase, UDPGT or UGT) is a microsomal glycosyltransferase () that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecu ...
in those with Gilbert syndrome. The cause for the increased risk of schizophrenia is not yet fully understood and is the object of further research.


Cause

Mutations in the ''UGT1A1'' gene lead to Gilbert Syndrome. The gene provides instructions for making the bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme, which can be found in the liver cells and is responsible for preparing bilirubin for removal from the body. The bilirubin-UGT enzyme performs a chemical reaction called
glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...
.
Glucuronic acid Glucuronic acid (GCA, from ) is a uronic acid that was first isolated from urine (hence the name "uronic acid"). It is found in many natural gum, gums such as gum arabic ( 18%), xanthan, and kombucha tea and is important for the metabolism of ...
is transferred to unconjugated bilirubin, which is a yellowish pigment made when your body breaks down old red blood cells, and then being converted to conjugated bilirubin during the reaction. Conjugated bilirubin passes from the liver into the intestines with bile. It's then excreted in stool. People with Gilbert syndrome have approximately 30 percent of normal bilirubin-UGT enzyme function, which contributes to a lower rate of
glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...
of unconjugated bilirubin. This substance then accumulates in the body, causing mild
hyperbilirubinemia Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
.


Genetics

Gilbert syndrome is a
phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
effect, mostly associated with increased blood bilirubin levels, but also sometimes characterized by mild jaundice due to increased
unconjugated bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
, that arises from several different genotypic variants of the gene for the enzyme responsible for changing bilirubin to the conjugated form.Beutler K, Lewandowski J. Gilbert's syndrome - bright and dark sides of the disease - literature review. Journal of Education, Health and Sport. 2024;63:146-154. doi:10.12775/JEHS.2024.63.011 Gilbert's syndrome is characterized by a 70–80% reduction in the
glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...
activity of the enzyme (UGT1A1). The ''UGT1A1'' gene is located on human chromosome 2. More than 100 polymorphisms of the ''UGT1A1'' gene are known, designated as ''UGT1A1*n'' (where n is the general chronological order of discovery), either of the gene itself or of its
promoter region In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of it ...
. ''UGT1A1 ''is associated with a
TATA box In molecular biology, the TATA box (also called the Goldberg–Hogness box) is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has a ...
promoter region; this region most commonly contains the genetic sequence A(TA)6TAA; this variant accounts for about 50% of
allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...
s in many populations. However, several allelic polymorphic variants of this region occur, the most common of which results from adding another dinucleotide repeat TA to the promoter region, resulting in A(TA)7TAA, which is called ''UGT1A1*28''; this common variant accounts for about 40% of alleles in some populations, but is seen less often, around 3% of alleles, in Southeast and East Asian people and Pacific Islanders. In most populations, Gilbert syndrome is most commonly associated with
homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...
A(TA)7TAA alleles. In 94% of GS cases, two other
glucuronosyltransferase Uridine 5'-diphospho-glucuronosyltransferase ( UDP-glucuronosyltransferase, UDPGT or UGT) is a microsomal glycosyltransferase () that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecu ...
enzymes,
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 lipophil ...
(rendered 50% inactive) and UGT1A7 (rendered 83% ineffective), are also affected. However, Gilbert syndrome can arise without
TATA box In molecular biology, the TATA box (also called the Goldberg–Hogness box) is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has a ...
promoter polymorphic variants; in some populations, particularly healthy Southeast and East Asians, Gilbert's syndrome is more often a consequence of
heterozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...
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 Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrat ...
.


Diagnosis

Gilbert syndrome is typically diagnosed based on clinical findings and laboratory results, emphasizing the exclusion of other potential causes of elevated bilirubin levels. The key criteria include: # Mild, Unconjugated Hyperbilirubinemia: #* Total serum bilirubin levels are mildly elevated, typically remaining below 6 mg/dL (102 μmol/L), with a predominance of the unconjugated (indirect) fraction. # Normal Liver Function Tests: #* Liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are within normal ranges, indicating no underlying liver disease. # Absence of Hemolysis: #* No evidence of increased red blood cell breakdown, as indicated by normal hemoglobin levels and reticulocyte counts. # Intermittent Nature of Symptoms: #* Episodes of jaundice that may be triggered by factors such as fasting, illness, stress, or exertion, with no other associated symptoms. The level of total bilirubin is often further increased if the blood sample is taken after
fasting Fasting is the act of refraining from eating, and sometimes drinking. However, from a purely physiological context, "fasting" may refer to the metabolic status of a person who has not eaten overnight (before "breakfast"), or to the metabolic sta ...
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, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ...
: the bilirubin will decrease substantially. # Exclusion of Other Liver Disorders: #* No clinical or laboratory evidence of other liver diseases; imaging studies and serologic tests for hepatitis are negative. # Genetic Testing: #* Identification of mutations in the UGT1A1 gene can confirm the diagnosis of Gilbert syndrome. While not routinely required, genetic testing may be considered in cases where the diagnosis is uncertain or to provide reassurance to patients.


Differential diagnosis

While Gilbert 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: * In Gilbert syndrome, unless another disease of the liver is also present, the liver enzymes ALT/SGPT and AST/SGOT, as well as
albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...
, are within normal ranges. *
Crigler–Najjar syndrome Crigler–Najjar syndrome is a rare inherited autosomal recessive disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of the heme in red blood cells. The disorder results in a form of non hemolytic jaundice, whic ...
(types I and II), a different glucuronyl transferase disorder, is much more severe, with 0–10% UGT1A1 activity, with affected individuals at risk of brain damage in infancy (type I) and teenage years (type II). *
Hemolysis Hemolysis or haemolysis (), also known by #Nomenclature, several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may ...
of any cause can be excluded by a full blood count, haptoglobin,
lactate dehydrogenase Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of pyruvic acid, pyruvate to lactic acid, lactate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that t ...
levels, and the absence of reticulocytosis (elevated reticulocytes in the blood would usually be observed in haemolytic anaemia). *
Dubin–Johnson syndrome Dubin–Johnson syndrome is a rare, autosomal recessive, benign disorder that causes an isolated increase of conjugated bilirubin in the serum. Classically, the condition causes a black liver due to the deposition of a pigment similar to melanin ...
and
Rotor syndrome Rotor syndrome (also known as Rotor type hyperbilirubinemia) is a rare cause of mixed direct (conjugated) and indirect (unconjugated) hyperbilirubinemia, relatively benign, autosomal recessive bilirubin disorder characterized by non-hemolytic jaun ...
are rarer
autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosome ...
recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
disorders characterized by an increase of conjugated bilirubin. * Viral hepatitis associated with increase of conjugated bilirubin can be excluded by negative blood samples for antigens specific to the different hepatitis viruses. *
Cholestasis Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are: * obstructive type of cholestasis, where there is a mechanical blockage in the duct system that can occur from a gallston ...
can be ''excluded'' by normal levels of bile acids in plasma, the absence of
lactate dehydrogenase Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of pyruvic acid, pyruvate to lactic acid, lactate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that t ...
, low levels of conjugated bilirubin, and
ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...
scan of the bile ducts. *
Vitamin B12 deficiency Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of Vitamin B12, vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have fe ...
- elevated
bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
levels (and MCV counts above 90–92) can be associated with a
vitamin B12 deficiency Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of Vitamin B12, vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have fe ...
.


Treatment

Gilbert's syndrome is a benign condition that typically requires no medical treatment. The primary approach involves patient education and reassurance about the harmless nature of the syndrome. Episodes of jaundice, when they occur, are usually mild and resolve on their own without intervention. To minimize the frequency of these episodes, individuals are advised to avoid known triggers such as fasting, dehydration, stress, and strenuous physical exertion. Maintaining a healthy lifestyle, including regular meals and adequate hydration, can help manage the condition effectively. If jaundice is significant
phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ...
may be used.


Research directions


Vitamin levels

Studies conducted so far suggest that subjects with GS may have lower levels of vitamin D and folic acid than control subjects, having these levels inversely correlated with bilirubin levels. It may be that GS may impair the metabolism or absorption of these vitamins, or that these vitamins may affect the expression or activity of the UGT1A1 enzyme that is responsible for bilirubin conjugation. However, these studies had limitations, such as the small sample size, the lack of a standardized definition of GS, the possible confounding factors of diet, lifestyle, and medication use, and the cross-sectional and observational design that does not allow for causal inference.


The role of bilirubin in health and disease

Ongoing studies suggest that mild hyperbilirubinemia in GS may have beneficial effects, probably due to the antioxidant and anti-inflammatory properties of bilirubin. Hyperbilirubinemia in GS may protect against oxidative stress and inflammation-related diseases, such as cardiovascular diseases, cancers, diabetes, and neurodegenerative disorders. However, the mechanisms and pathways of bilirubin protection are not fully elucidated, and the optimal level and range of bilirubin are unknown. The genetic and environmental factors that influence UGT1A1 expression and activity are also poorly characterized and may affect the variability and penetrance of GS. Despite the fact that hyperbilirubinemia in GS is associated with reduced incidence of cardiovascular diseases, diabetes, and metabolic syndrome, the clinical significance and implications of these GS research findings are unclear, and can not yet be translated into preventive or therapeutic strategies.


History

Gilbert syndrome was first described by French gastroenterologist
Augustin Nicolas Gilbert Augustin Nicolas Gilbert (; 15 February 1858 – 4 March 1927) was a French physician. He was born in the town of Buzancy, Ardennes, and died in Paris. He received his doctorate from the University of Paris and became an intern at the Hôtel-Die ...
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


Society and culture


Notable cases

*
Napoleon Napoleon Bonaparte (born Napoleone di Buonaparte; 15 August 1769 – 5 May 1821), later known by his regnal name Napoleon I, was a French general and statesman who rose to prominence during the French Revolution and led Military career ...
*
Arthur Kornberg Arthur Kornberg (March 3, 1918 – October 26, 2007) was an American biochemist who won the Nobel Prize in Physiology or Medicine in 1959 for the discovery of "the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic a ...
, Nobel laureate in Physiology or Medicine, 1959 *
Nicky Wire Nicholas Allen Jones (born 20 January 1969), known as Nicky Wire, is a Welsh musician, best known as lyricist, bassist and secondary vocalist of the Welsh alternative rock band Manic Street Preachers. Prior to the group, Wire studied politics ...
,
Manic Street Preachers Manic Street Preachers, also known simply as the Manics, are a Wales, Welsh Rock music, rock band formed in Blackwood, Caerphilly, in 1986. The band consists of Nicky Wire (bass guitar, lyrics) and cousins James Dean Bradfield (lead vocals, le ...
bassist *
Alexandr Dolgopolov Alexandr Oleksandrovych Dolgopolov (born 7 November 1988), formerly known as Oleksandr Dolgopolov Jr., is a Ukrainian retired professional tennis player. He changed his forename spelling to the current form in May 2010. Dolgopolov reached the qu ...
(tennis player) * Jonas Folger,
MotoGP Grand Prix motorcycle racing is the highest class of motorcycle road racing events held on Road racing, road circuits sanctioned by the Fédération Internationale de Motocyclisme (FIM). Independent motorcycle racing events have been held sin ...
rider.


References


External links


Understanding Gilbert's Syndrome and living better with Gilbert's Syndrome symptoms
*

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Best Practices monograph {{DEFAULTSORT:Gilbert's Syndrome Accessory digestive gland disorders Hepatology Heme metabolism disorders Genetic syndromes Pediatrics Wikipedia medicine articles ready to translate