Hepatocerebral dystrophy.

Wilson-Konovalov disease, or hepatocerebral dystrophy, is a hereditary pathology in which damage to the liver and nervous system is observed. The disease is inherited in an autosomal recessive manner, with the pathogenic gene located in the q-arm of the thirteenth chromosome.

Copper metabolism disorder plays the main role in the etiology of the disease. Copper accumulates in excessive amounts in liver tissue, in the brain, in the urinary system, and in the cornea. The incidence rate is 0.3:10,000.

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Causes of hepatocerebral dystrophy

The disease is caused by a hereditary disorder of copper metabolism. Specialists detect a marked increase in copper content in the body structures. At the same time, copper excretion through the urinary system increases. At the same time, its content in the bloodstream decreases.

Failures in the mechanism of microelement distribution occur due to a genetically dependent decrease in the amount of ceruloplasmin, a specific copper-containing plasma protein. Copper, which enters the bloodstream from food, cannot remain 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 in increased volumes by the kidneys.

The accumulation of copper in the renal tissue provokes a disorder in the functioning of the urinary filtration system, which, in turn, leads to the appearance of aminoaciduria (aminoaciduria).

Impaired brain function, damage to liver and corneal tissue are also associated with increased accumulation of copper in them.

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Symptoms of hepatocerebral dystrophy

The disease manifests itself more often in the age period from ten to 25 years. The main symptoms of the pathology are considered to be muscle weakness, tremors and increasing dementia. Muscle weakness can manifest itself in varying degrees. Sometimes the characteristic Parkinsonian syndrome affects the entire muscular system. The face takes on the appearance of a mask, the lower jaw hangs down, attempts to speak are slurred, the voice becomes alien, muffled. At the same time, swallowing may be impaired due to the relaxation of the pharyngeal muscles. Salivation increases. Motor activity is inhibited. Arms and legs may freeze in non-standard and even strange positions.

Against the background of muscle weakness, noticeable tremors appear, especially pronounced in the upper limbs (the so-called wing flaps). Such movements may disappear during periods of rest and suddenly appear when moving the arms to the sides or raising them to the level of the shoulder girdle. Tremors may appear on one hand or on both at the same time, as well as on the fingers in the form of spasms.

In the later stages of the disease, epileptic seizures may occur, the patient may fall into a coma. A decrease in mental abilities is observed, up to significant mental disorders.

The sensitivity of the skin and limbs is not affected. Tendon reflexes may even increase somewhat - sometimes the Babinski reflex can be recorded (pathological extension of the big toe with deliberate irritation of the sole of the foot).

A characteristic feature of hepatocerebral dystrophy, which is a direct symptom of the disease in about 65% of patients, is the so-called corneal Kayser-Fleischer ring. This is a pigmented line of a brown-greenish hue, passing along the posterior region of the cornea, bordering the sclera. Such a line can be observed during a routine examination or with the help of a slit light.

In the laboratory, one can see the development of anemia, thrombocytopenia and other blood composition disorders – all of this is a consequence of liver dysfunction.

Diagnosis of hepatocerebral dystrophy

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

Main signs for diagnosis:

• symptoms of simultaneous damage to the brain and liver;
• unfavorable heredity of an autosomal recessive type;
• initial manifestations of the disease after 10 years of age;
• extrapyramidal disorders (tremors, weakness, inadequate position of the body and limbs, spastic pain, movement disorders, swallowing, decreased mental capacity);
• extraneural disorders (pain in the right hypochondrium, tendency to bleeding, joint pain, damage to tooth enamel and gums);
• presence of a corneal ring;
• decrease in ceruloplasmin levels;
• increased excretion of copper through the kidneys;
• DNA diagnostics.

The disease is differentiated from muscular dystonia, parkinsonism, and multiple sclerosis.

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Treatment of hepatocerebral dystrophy

Treatment of the disease is based on the fact that pathological disorders in the body manifest themselves as a consequence of an increased amount of copper in the bloodstream. It is recommended to follow a diet that includes the exclusion of foods with a high copper content from the diet. Chocolate, cocoa products, any nuts and mushrooms, and liver are prohibited.

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

Treatment with penicillamine (synonym – cuprenil) is carried out according to the following scheme:

• At first, 150 mg of the drug is prescribed every day for a week;
• during the second week, take 150 mg daily;
• then the daily dose of the drug is increased by 150 mg weekly. This is done until the excretion of copper by the kidneys reaches 1-2 g.

Once the patient's condition improves, a maintenance dose of 450 to 600 mg per day is prescribed. The amount of vitamin B6 taken should be 25 to 50 mg daily.

If severe side effects (allergies, nausea, kidney disease, etc.) occur during treatment, penicillamine is discontinued for a while, after which a switch is made to low doses of the drug simultaneously with 20 mg of prednisolone per day (for 10 days).

If the patient has an intolerance to penicillamine, 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, unfortunately, it is impossible to warn and prevent it. During medical genetic consultations, parents who have a child with dystrophy are advised to give up trying to have children in the future. A heterozygous carrier of a mutated gene can be detected using biochemical tests: counting the amount of ceruloplasmin in the blood serum, as well as the degree of excretion of amino acids and copper through the kidneys.

It is important to detect the disease as early as possible, which will allow the patient to remain active for a long time and slow down the development of irreversible consequences in the brain. Regular use of penicillamine is a kind of guarantee of extending the patient's full life.

Prognosis of hepatocerebral dystrophy

The course of the disease is recognized by specialists as certainly progressive. The duration of a patient's full life may depend on the number and degree of symptoms, as well as on how timely the treatment was started. The average life expectancy of patients without treatment is approximately 6 years, and in the case of an aggressive malignant course of the disease - several months and even weeks.

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