Gilbert syndrome - Causes, symptoms and treatment. MF.

Gilbert syndrome is a genetic disease characterized by impaired bilirubin utilization. The liver of patients improperly neutralizes bilirubin, and it begins to accumulate in the body, causing various manifestations of the disease.

Gilbert syndrome was first described by the French gastroenterologist - Augustine Nicolas Gilbert( 1958-1927) and his colleagues in 1901.This pathology has several names: family non-hemolytic jaundice, benign family jaundice, constitutional liver dysfunction or Gilbert's syndrome. It occurs as a result of an increase in the amount of unconjugated bilirubin in the blood plasma, without signs of liver damage, obstruction of the biliary tract or hemolysis. This disease is family and is inherited. The disease occurs due to a genetic defect, which leads to a disruption in the formation of an enzyme that facilitates the utilization of bilirubin. People with Gilbert syndrome have a moderately elevated level of bilirubin in the blood, which can sometimes cause jaundice sclera of the eyes and skin. Gilbert's syndrome does not require radical treatments. Since this syndrome has a small number of symptoms and manifestations, it is not considered a disease, and most people do not know that they have this pathology, until a blood test shows an elevated level of bilirubin. In the United States of America, approximately 3% to 7% of the population have Gilbert's syndrome, according to the National Institutes of Health - some gastroenterologists believe that the prevalence may be greater and reach 10%.The syndrome manifests itself more often among men.

The cause of Gilbert's syndrome.

The main functions of the liver

The liver is the largest organ of the human body. Some of the key liver functions:
• Converts thyroxine thyroid hormone( T4) into a more active form of triiodothyronine( T3).Insufficient conversion can lead to hypothyroidism, chronic fatigue, weight gain, poor memory and the appearance of other symptoms.
• Creates GTF( glucose tolerance factor) from chromium, niacin and, probably, glutathione. GTF is needed for insulin to properly regulate blood sugar levels.
• The liver synthesizes bile salts, which emulsify fats and fat-soluble vitamins A, D, E, K for better assimilation. The liver also removes some fat-soluble toxins from the body.
• Activation of vitamins in their biologically active forms - coenzymes. Almost every nutrient must be biotransformed in the liver in the proper biochemical form before storing, transferring or integrating into metabolic processes.
• Accumulation of nutrients, especially vitamins A, D, B-12 and iron for consumption as needed.
• Produces carnitine from lysine and other nutrients. Carnitine is the only known bio-nutrient that can transport fats to the mitochondria where they are used to generate ATP energy. Mitochondria generate 90% of the energy of ATP at the cellular level.
• The main regulator of protein metabolism. The liver turns different amino acids into each other as needed.
• Produces cholesterol and converts it into various forms needed to transport substances to tissues.
• The detox function is one of the most important functions of the liver. Most harmful substances and metabolic products are neutralized in the liver. So the decay products of the cellular elements of the body, undergo a series of transformations, in particular products of erythrocyte decay.

Hyperbilirubinemia - increased blood levels of bilirubin - occurs because the activity of the enzyme glucuronyltransferase, which conjugates bilirubin, is reduced. Neutralization, which takes place in the liver, makes bilirubin soluble in water, so that it can dissolve into the bile and enter the duodenum, and ultimately withdraw from the body. The average life span of the red blood cell is 120 days, after which it is disposed of and broken down into bilirubin and hemoglobin. Directly in the liver, the insoluble form of bilirubin is converted to a water-soluble form. Gilbert syndrome causes a gene defect - a mutation of UDP-glucuronosyltransferase, a gene responsible for the production of this enzyme. People inherit the syndrome from their parents. Bilirubin is not neutralized and accumulates in the blood. When the level reaches a certain point, the patient may experience symptoms of jaundice.

Symptoms of Gilbert's syndrome

Most people who suffer from the disease do not know that they have it. The level of bilirubin usually remains within the normal range, and sometimes slightly increases. One of the earliest and pathognomonic symptoms is jaundice. Yellowness of the sclera or skin may appear, when the amount of bilirubin in the blood rises. Symptoms may increase and become more apparent in combination with: another disease, infection, dehydration, stress, or menstruation. Although the level of bilirubin is unlikely to ever reach dangerous numbers, jaundice is one of the important and alarming symptoms.

Jaundice of the skin( left-normal, right-pathology)

Jaundice sclera

The following symptoms can also be pathognomonic, but to a lesser extent. Often patients describe fatigue, clouded consciousness, headaches, memory impairment, dizziness, depression, irritability, anxiety, nausea, loss of appetite, irritable bowel syndrome, abdominal pain and cramps, pain in the liver / gall bladder, tremor, itching of the skinpokrovov. Vozmozhno occurrence of insomnia, difficulty in concentration of attention, panic attacks, hypoglycemic reaction to food, intolerance to carbohydrates, alcohol.

Food intolerance can cause loose stools or diarrhea, bloating. Symptoms of respiratory and heart failure may appear: shortness of breath or shallow breathing, palpitations. Because of metabolic disorders, there is pain in the muscles and joints, weakness, weight loss and perversion of taste.

The following symptoms( very rare and with a marked violation of bilirubin metabolism), which require urgent medical intervention: difficulty in word selection, feelings of intoxication, indomitable vomiting, excessive thirst, chest pain, muscle twitching( tremor), enlarged lymph nodes, bitter or metallic taste in the mouth. These symptoms indicate the development of acute liver failure.

Diagnosis of Gilbert's Syndrome

This diagnosis is most often exhibited in the late adolescent period. The diagnosis is made easily, if the history of the disease is correctly collected, genetic typing in this case is not necessary. The patient takes a blood sample, which examines the liver function and the level of direct and indirect bilirubin. If the results of the analysis show a high level of insoluble bilirubin in the blood, and other indicators are normal, the doctor can diagnose Gilbert's Syndrome. In the presence of severe jaundice, a number of differential diagnostic tests may be required to exclude other pathologies that may be, for example:

1. Acute inflammatory liver diseases( hepatitis) - they can worsen the ability of the liver to utilize bilirubin.
2. Inflammation of the bile ducts - can interfere with the secretion of bile and the removal of bilirubin.
3. Biliary duct obstruction also interferes with bile flow and contributes to the accumulation of bilirubin.
4. Hemolytic anemia - leads to an increase in bilirubin due to increased disintegration of erythrocytes.
5. Cholestasis - the flow of bile from the liver is interrupted. Bile containing bilirubin remains in the liver.
6. Kriegler-Najjar syndrome - congenital non-hemolytic unconjugated bilirubinemia.
7. Dabin-Johnson syndrome is an enzymatic jaundice, a rare pigmentary hepatosis characterized by impaired excretion of bound bilirubin from hepatocytes into bile capillaries.
8. False jaundice is an inoffensive form of jaundice, in which yellowing of the skin is associated with an excess of beta-carotene.

Additional tests may include: ultrasound scanning of the abdominal cavity to exclude obstruction of the biliary tract or diffuse pathology of the liver, diet for 24 hours to exclude the alimentary cause of bilirubin increase and genetic typing.

Treatment of Gilbert's syndrome.

Gilbert syndrome is considered a harmless disease - usually does not cause any health problems. At the moment there is no effective etiotropic treatment for the development of medical technologies. Although the symptoms of jaundice can be of concern to the patient, the doctor should explain that jaundice is not a regular symptom, and should not cause concern. Long-term follow-up of a patient with Gilbert's syndrome is usually not required. If the patient notices a worsening of the symptoms of jaundice, he should tell his doctor about it so that he can rule out other various causes. Patients in whom the symptoms of jaundice cause severe anxiety can take in small amounts of phenobarbital. It has a slight antihyperbilirubinemic effect. Along with its positive effect, this drug causes a sedative effect on the nervous system, and with prolonged use causes toxic effects on the liver. Therefore, an effective and balanced dosing of this drug is important.

The diet can alleviate the symptoms: products with a long shelf life and containing a large number of preservatives should be excluded from the diet, multivitamin complexes should be used to strengthen the overall immunity, all products should be boiled, baked or cooked on steam( minimum fat).

Complications of Gilbert's syndrome

Gilbert's syndrome alone does not cause any complications and does not damage the liver, but it is important in time to differentiate one kind of jaundice from another. In this group of patients, the sensitivity of the liver cells to hepatotoxic factors, such as alcohol, drugs, and certain groups of antibiotics, was noted. Therefore, in the presence of the above-described factors, it is necessary to monitor the level of hepatic enzymes.

Doctor therapist Zhumagaziev E.N.