Gilbert`s syndrome (GS) is an inherited liver disorder in which there is incomplete elimination of bilirubin from the body leading to elevated bilirubin levels called as hyperbilirubinemia. It occurs due to reduced levels of specific liver enzyme and has autosomal recessive inheritance. The disease is generally asymptomatic or exhibit mild jaundice post physiological or psychological stress. Mostly, medical treatment is not required.
The disorder usually presents in the form of unconjugated hyperbilirubinemia. Clinically, apart from jaundice, patients have normal physical examination. In diseased children or adults, the condition usually manifests under stressful conditions like fasting, exposure to cold, dehydration or infections.
Newborns with GS experience more severe and longer lasting form of neonatal jaundice shortly after birth. As the condition is benign, it usually goes undetected until it is accidentally found in the form of elevated blood levels of bilirubin during a routine check up. In such individuals, bilirubin levels are elevated and fluctuates between 34 and 86 μmol/L (2 and 5 mg/dl). They tend to rise under stressful conditions like fasting. The bilurubin level in diagnosed cases of Gilbert syndrome is defined to be lower than 6 mg/dl, though, most patients have levels lower than 3 mg/dl. Approximately 30% of the patients are asymptomatic. Besides jaundice, they don't show any other symptom. Certain non-specific symptoms like fatigue, malaise and abdominal cramps can occur in these patients.
In some cases, mild stomach ache and nausea may be present during the episode of hyperbilirubinemia. However, presence of gastrointestinal ailments listed above is not directly related to increased levels of bilirubin in blood. It is often manifested as a psychological side effect in patients following the diagnosis of the disease. The bilirubin levels may show daily and seasonal fluctuations and in nearly one third patients the levels may occassionally be found to be normal.
Gilbert syndrome may become apparent immediately after the birth, however, it may take several years to recognize this condition. Jaundice episodes are more common in males than females. In many individuals, it becomes prominent only under certain triggering conditions such as dehydration, fasting, stress, infection, strain or exposure to cold. Some of the patients complain about stomach cramps, exhaustion and slight depression. However, there is no scientific evidence to connect these ailments. Anesthesia and surgery are the other two stressful events which can possibility bring about a hike in bilirubin levels post operation .
Diagnosis of Gilbert syndrome is made from thorough history and physical examination and is confirmed by specific blood tests. Clinical features, triggering factors and disease duration helps in making the diagnosis clinically. Frequently the diagnosis is made following blood tests during a routine health check up or another medical illness.
Confirmation of hyperbilirubinemia by blood test along with no incidence of hemolysis (pathological destruction of erythrocytes) is suggestive of the condition. Patients have a normal liver function and hyperbilirubinemia is usually mild with a bilirubin level less than 6 mg/dl. Bilirubin level often fluctuates and as a consequence the bilirubin level may sometimes not reflect the condition. Periodic clinical examinations and surgical procedures are not advised for disease confirmation in clinical practice. One time confirmatory test include
These tests are not recommended for diagnosis in the newborn due to high risk of toxicity from the drugs. Developed countries follow certain specific genetic studies through laboratory investigation to confirm diagnosis of disease in suspected cases.
No medical intervention is required in the management of Gilbert syndrome. The most important part in the disease management is assuring patients regarding the benign condition of the disease and the association of normal life expectancy. Clear instructions should be given to them regarding the conditions that can trigger the symptoms i.e. jaundice such as stress, dehydration, fasting, exposure to cold, etc. Owning to benign and harmless nature of GS associated mild jaundice, the condition resolves spontaneously without any medical therapy.
GS is a commonly occurring benign condition which has an excellent prognosis. In most of the cases, the concentration of unconjugated bilirubin is found to be under normal range. Approximately one third of the normal UGT1A1 activity is retained in the patients that cause enough conjugation of bilirubin to produce any symptoms. The condition doesn't have any detrimental effect on the diseased individuals who generally lead a healthy normal life style. The benign nature of the disorder is further proved by studies on patients who underwent liver transplantation from live donors diagnosed to have Gilbert syndrome  .
Genetically, it develops as a result of mutations in the UGT1A1 gene in the long arm (q) of chromosome 2 (2q37) which codes for bilirubin-UGT. Gilbert syndrome is a form of non-hemolytic jaundice, which is inherited in an autosomal recessive fashion. Being recessive, it occurs when an individual acquires the mutated gene from both the parents. An individual is considered as "carrier" when he/she receive the defective gene from one parent and a normal gene from other parent. In a carrier, the disorder is not expressed and the person remains normal with full functionality of bilirubin-UGT and bilirubin metabolism. However the carrier person is capable of passing on the defective gene to his/her offspring. The probability of an offspring to inherit the defective gene from two carrier parents is about 25% and in about 50% of the cases the child ends up being a carrier like his/her parents. The risk of acquiring the disease is equal for both male and female.
GS is not an uncommon disorder that affects around 2 to 13 % of the general population  . The disease is the mildest form of inherited nonhemolytic unconjugated hyperbilirubinemia . Though the risk is the same for both sexes, it is found more commonly in males. There is no racial preponderance in GS. It is a genetic, congenital disorder which mostly remains undetected until early adulthood. Though family members may be affected, it is difficult to get a clear pattern of genetic inheritance. The condition is usually diagnosed and become evident with detection of elevated levels of unconjugated bilirubin in blood without any apparent reason.
Bilurubin is an end product of human red blood cell breakdown. It has an orange-yellow color and is removed from the body only in the conjugated form. In the liver, toxic unconjugated bilirubin is changed into non-toxic conjugated form. In patients with Gilbert syndrome, there occurs an increased level of unconjugated bilirubin in the blood. Though, these levels fluctuate and rarely reach enough to produce the symptoms such as yellowing of the skin and eyes.
Pathogenesis of GS involves defects in the uptake of bilirubin by the liver which occurs due to low Glucuronyl transferase activity. In some patient's destruction of RBC's is also accelerated, though, it doesn't explain the hyperbilirubinemia. There is around 30% decrease in the activity of hepatic bilirubin UGT in patients with GS. However, it should be noted that the enzyme activity is not as low as that observed in cases of type 2 Crigler-Najjar syndrome. A drop is indicated by the presence of relatively increased concentration of monoconjugates of bilirubin in the bile. The Liver, however, shows histology.
In the promoter region of the UGT-1TA gene, expansion of thymine-adenine (TA) repeat units occur. This gene provides the instruction for coding of uridine disphosphate-glucronosyltransferase-1A1 enzyme which is involved in the conversion of unconjugated bilirubin to conjugated form. The difference in the total number of TA repeats in the gene is found to be related to the activity of UGT1A1 enzyme.
In affected patients, hepatocytes fail to take up the unprocessed bilirubin leading to its accumulation in the blood plasma as unconjugated bilirubin (bound to albumin). The bilirubin-albumin product is insoluble in water. In normal individuals, unconjugated bilirubin is converted to conjugated form which is water soluble and is excreted into the bile in the liver. The bile produced is temporarily retained in the gall bladder and is then transferred to the duodenum (the upper part of the small intestine) via the common bile duct. Most of the bilirubin is excreted from the body through the feces. In asymptomatic individuals, UGT1A1 enzyme maintains one third of its activity to detoxify enough uncongugated bilirubin so that no symptoms develop. However under stressful conditions like fasting and dehydration patients may develop mild form of jaundice. Presence of bilirubin monoconjugates in high levels in the bile indicates reduced activity of transferase enzyme    .
Most patients of Gilbert syndrome are asymptomatic. However, certain conditions can lead to aggravation of the clinical jaundice and hence need to be avoided. These conditions are stress, dehydration, fasting , infection, extreme weather conditions, fatigue, menstruation , alcohol, etc. Unavoidable stressful events like surgical procedures and anesthesia  may sometimes lead to an episode of jaundice during or after operation and therefore adequate measures.
Gilbert`s syndrome (GS) is an inherited life long disease affecting the liver with mild or no symptoms. The affected individuals lack the liver enzyme, bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT) which is responsible for proper disposal of bilirubin. The only characteristic finding is unconjugated hyperbilirubinemia leading to jaundice, which presents as a yellowish discolouration of skin and eyes sclera. Jaundice may sometimes mistaken for other liver disorders or chronic hepatitis leading to incorrect diagnosis. The condition may go undetected until early adulthood and noticed accidentally during routine blood check up. The affected individuals often have high levels of bilirubin in the blood with no apparent symptoms. The condition generally does not require any medical interventions and the patient should be advised to avoid situations that trigger an episode of jaundice. The major physiological triggers to avoid include stress,dehydration, infections, excessive physical exertion and fasting.
Gilbert syndrome (GS) is a condition characterized by increased bilirubin concentration in the blood. The toxic form of bilirubin called as unconjugated bilirubin is converted to non toxic conjugated bilirubin in the liver and is subsequently eliminated from the body via the gastrointestinal tract under normal conditions. In case of affected individuals, this does not happen as efficiently as in normal individuals. However, it should be noted that it is not a liver disorder and is therefore a harmless condition requiring no medical therapy in a majority of the cases. The condition has a very good prognosis. The life expectancy is normal and is not associated with any increased mortality. However, care should be taken while taking certain drugs such as irinotecan, an antitumor agent which are associated with an increased morbidity due to increased side effects in patients with Gilbert syndrome.
The bilirubin level keeps fluctuating and when rises beyond a particular level manifest in the form of jaundice. Yellowing of skin and eyes are the major symptoms. The condition usually goes unnoticed during childhood and is accidentally diagnosed later in adolescence. The condition is usually aggravated during stressful periods of life like illness, during menstrual cycle, fasting, dehydration, fever, surgeries involving anesthesia and fasting, repeated illness or vigorous exercise . Extended periods of fasting induce jaundice due to the presence of fatty acids that hinder the normal bilirubin excretory mechanism. In some cases jaundice is accompanied by mild abdominal pain and fatigue. These discomforts along with jaundice usually disappear spontaneously without any medical intervention.