Hepatocerebral dystrophy

Wilson-Konovalov's disease, or hepatocerebral dystrophy is a hereditary pathology, in which liver and nervous system damage is observed. The disease is inherited by an autosomal recessive type, while the pathogen gene is located in the q-arm of the thirteenth chromosome.

In the etiology of disease, the main role is played by the disorder of copper metabolism. Copper in excessive amounts accumulates in liver tissues, in the brain, in the urinary system, in the cornea. The incidence rate is 0.3: 10,000.

[1], [2], [3], [4], [5], [6]

Causes of hepatocerebral dystrophy

The appearance of the disease is due to a hereditary disorder of copper metabolism. In the structures of the body, specialists show a marked increase in the copper content. At the same time, the excretion of copper through the urinary system increases. At the same time, its content in the blood stream decreases.

Failures in the mechanism of microelement distribution occur due to a genetically dependent decrease in the number of ceruloplasmin - a specific copper-containing plasma protein. Copper, which enters the bloodstream from food, can not stay in the blood, because the content of copper-containing protein is reduced. As a result, copper is forced to accumulate in various organs and tissues and is excreted by the kidneys in high volumes.

Accumulation of copper in the kidney tissue provokes a disruption of the urinary filtration system, which, in turn, leads to the appearance of aminoaciduria (amino acid).

Violations of brain functions, damage to liver tissue and cornea are also associated with increased accumulation of copper in them.

[7], [8], [9], [10], [11]

Symptoms of hepatocerebral dystrophy

The disease manifests itself more often in the age range of ten to 25 years. The main symptoms of the pathology are muscle weakness, trembling and increasing dementia. The weakness of the muscles can manifest itself in varying degrees. Sometimes a characteristic Parkinsonian syndrome captures the entire musculature system. The face takes on the form of a mask, the lower jaw hangs, attempts to speak are indistinct, the voice becomes, as it were, a stranger, deaf. At the same time, swallowing can be disturbed, because of the relaxation of the muscles of the pharynx. Increases salivation. Motor activity is inhibited. Hands and feet can freeze in non-standard and even strange positions.

Against the background of muscle weakness, there is a noticeable tremor, especially pronounced in the upper limbs (the so-called wing swings). Such movements can disappear during the rest period and suddenly appear when the arms are sideways or raised to the level of the shoulder girdle. Trembling can occur on one hand or on two at a time, as well as on the fingers in the form of spasms.

In the late stages of the disease, epileptic seizures may occur, the patient may fall into a coma. There is a decrease in mental abilities, down to significant mental disorders.

The sensitivity of the skin and limbs does not suffer. Reflexes of the tendons may even slightly increase - sometimes you can fix the reflex of Babinsky (abnormal extension of the thumb on the foot with deliberate stimulation of the sole of the foot).

A characteristic feature of hepatocerebral dystrophy, which is a direct symptom of the disease in approximately 65% of patients, is the so-called Kaiser-Fleischer corneal ring. It is a pigmented line of brownish-greenish tinge that runs along the posterior region of the cornea bordering the sclera. Such a line can be observed during normal inspection, or by means of a slit illuminator.

It is possible to see the development of anemia, thrombocytopenia and other malfunctions of the blood in the laboratory - all this is a consequence of a liver function disorder.

Diagnosis of hepatocerebral dystrophy

With a typical clinical picture, the diagnosis of the disease is not difficult. Evaluation of heredity, signs of damage to the subcortex (dystonia, hyperkinetic symptoms), Kaiser-Fleischer ring-all this already makes it possible to suspect hepatocerebral dystrophy. Confirm the diagnosis by determining a reduced amount of ceruloplasmin (a characteristic decrease of less than 1 μmol / L) in blood plasma and increased excretion of copper by urinary excretion (an increase greater than 1.6 μmol or 50 μg / day).

The main signs for diagnosis:

• symptoms of simultaneous brain and liver damage;
• adverse heredity by autosomal recessive type;
• initial manifestations of the disease after 10 years of age;
• extrapyramidal disorders (trembling, weakness, inadequate position of the body and extremities, spastic pain, movement disorders, swallowing, lowering of mental abilities);
• extra-neural disorders (pain in the right upper quadrant, tendency to bleeding, joint pain, damage to tooth enamel and gums);
• the presence of the corneal ring;
• a drop in the level of ceruloplasmin;
• increased excretion of copper through the kidneys;
• DNA diagnostics.

Differentiate the disease with muscular dystonia, Parkinsonism, multiple sclerosis.

[12], [13], [14], [15]

Treatment of hepatocerebral dystrophy

Treatment of the disease is based on the fact that pathological disorders in the body are manifested, as a consequence of the increased amount of copper in the bloodstream. It is recommended to adhere to a diet that provides for the exclusion from the diet of foods high in copper. Under the ban fall chocolate, products with cocoa, any nuts and mushrooms, liver.

Drug therapy provides for a long-term use of d-penicillamine, from 1.2 to 2 g of the drug every day. To date, this treatment is most effective: there is persistent clinical improvement and sometimes even a complete involution of symptoms. Such therapy is usually accompanied by taking medications with a high content of vitamin B6, as its content in tissues during treatment tends to decrease.

Treatment with penicillamine (synonym - kurrenyl) is carried out according to the following scheme:

• First time appoint 150 mg of the drug every day for a week;
• during the second week they take 150 mg daily;
• then weekly the daily amount of the drug is increased by 150 mg. This is done until the excretion of copper by the kidneys reaches 1-2 g.

After the patient's condition improves, a retention dosage of 450 to 600 mg per day is prescribed. The amount of vitamin B6 taken at this time should be from 25 to 50 mg daily.

If during the treatment there were significant side effects (allergy, bouts of nausea, kidney disease, etc.), then penicillamine is temporarily canceled, after which they switch to small dosages of the drug simultaneously with 20 mg of prednisolone per day (for 10 days).

If a patient has a penicillamine disapproval, then zinc sulfate is prescribed in the amount of 200 mg three times a day.

Prevention of hepatocerebral dystrophy

Since hepatocerebral dystrophy is a hereditary pathology, it is unfortunately impossible to prevent and prevent it. During medical genetic counseling, parents who have had a baby with dystrophy are later advised not to try to have children. The heterozygous carrier of a mutated gene can be detected by biochemical assays: counting the amount of ceruloplasmin in the blood serum, and the degree of excretion of amino acids and copper through the kidneys.

It is important that the earliest detection of the disease is possible, which will allow the patient to remain active for a long time and to slow down the development of irreversible consequences in the brain. Regular use of penicillamine is a kind of guarantee for prolonging the life span of the patient.

Prognosis of hepatocerebral dystrophy

The course of the disease is recognized by specialists as undoubtedly progressing. The duration of the patient's full life may depend on the number and extent of the symptoms, and on the timing of the treatment. The average life expectancy of patients in the absence of treatment is approximately 6 years, and in aggressive malignant course of the disease - several months and even weeks.

Hepatocerebral dystrophy has the most favorable prognosis only if the treatment was prescribed even before the appearance of signs of damage to the liver and nervous system.