Hepatolentikuljarnaja degeneration: why arises and as it is shown

The term hepatolenticular degeneration was proposed in 1912, when Wilson identified changes in lenticular nuclei of the brain in a disease affecting the nervous system and liver. By the time when the domestic scientist Konovalov determined the defeat of other departments of the nervous system, it was already known what role copper plays in the development of this disease. From this point on, the international classification uses the term hepatocerebral dystrophy (Wilson-Konovalov's disease).

Hepatocerebral dystrophy is a hereditary autosomal recessive disease, accompanied by a combined lesion of the central nervous system and liver as a result of a violation of copper metabolism.

Causes

Hepatolenticular degeneration is a genetic pathology, the essence of which is the violation of the synthesis of protein, which binds and transports copper.

At the heart of the disease is a genetic disruption of the synthesis of a special protein - ATP7B, which transports copper (Cu2 +) into cellular lysosomes and facilitates its binding to the enzyme ceruloplasmin.

Every day about 4 mg of copper enters the human body with food (beans, chocolate, etc.). The major part of the element in the blood binds to the ceruloplasmin protein, a small part is in a free state. Excess copper is excreted with bile through the intestine. With the genetic defect of ATP7B protein, the concentration of free Cu2 + increases and its excretion from the body is disturbed. Free copper in high concentrations has a toxic effect on organs and tissues, causing their damage and the corresponding symptoms of injury. The deposition of the element occurs in the liver, kidneys, the cornea of ​​the eyes, in the structures of the central nervous system: basal ganglia, deep layers of the cortex, cerebellum.

Manifestations of hepatolenticular degeneration

The clinical picture of hepatocerebral dystrophy is diverse due to the defeat of many organs. The classification proposed by Konovalov identifies one form of the disease with predominance of symptoms on the part of the liver and four forms of the disease with predominance of symptoms from the side of the central nervous system.

Abdominal form

The debut of the disease is at the age of 8-15 years, which manifests itself as a liver lesion by the type of hepatitis or cirrhosis. A child is disturbed by general weakness, malaise, decreased appetite, loss of body weight. There is icterus of skin and itching. The disruption of the liver leads to an inadequate synthesis of proteins, which is manifested by the development of edema, the accumulation of fluid in the abdominal cavity (ascites). In severe cases, a hepatic coma develops. Lethal outcome may occur before the onset of neurologic symptoms in the absence of treatment.

The early form (rigid-arrhythmogenic hypertension)

Symptoms of damage from the nervous system manifest themselves closer to 20 years of life and are associated with the release of excess copper from the hepatic cells into the systemic circulation and distribution throughout the body.

The clinical picture is diverse, but most of the symptoms are associated with the lesion of the extrapyramidal system, which includes the basal ganglia, the cerebellum.

With this form of the disease, the development of muscle rigidity with contractures is at the forefront. Muscle rigidity is a stiffness of movements due to increased muscle tone. A person has resistance when trying to passive movements in the joints. For example, when you try to unbend your arm at the elbow joint or straighten your head, there is resistance and pain. Half-bent position with time is fixed by contractures (contraction).

The patient is formed torsion-dystonic movements. These are movements that arise as a result of muscle spasms and the rotation of the spasmodic part of the body around its axis: bizarre bending of the hands, curvature of the trunk, turning of the head,

Torsion dystonia is enhanced by trying to move, performing manipulations, leading to a person's falls. There may be large-scale movements in the hands, an elaborate position of the fingers in the hands and feet.

An asthmatic-rigid form

There is a simultaneous trembling (tremor) of parts of the body and muscle rigidity. The person's walk becomes shaky, accompanied by falls. Violation of the pronunciation of sounds and words - dysarthria, changing the tone of the voice - dysphonia. There are sweeping movements in the arms and legs. When trying to focus the movements (writing, playing on instruments, etc.) tremors increase. The throbbing-rigid form is more often detected at the age of 15-20 years.

Throbbing form

A person is worried about a tremor that increases when trying to hold hands or feet in a certain position. Muscular rigidity is absent in this form of the disease. The debut of the disease with a trembling form occurs at the age of 20-30 years.

Extrapyramidal-cortical form

This form of the disease is manifested by paresis (weakness) in the hands, in the legs. Simultaneously, epileptic seizures join.

Over time, a person is diagnosed with mental disorders. These can be attacks of anger, a decrease in mental abilities, a sharp change in mood, a decrease in the criticism of one's behavior.

Other manifestations

Copper is deposited in the cornea of ​​the eye, resulting in a pigmentation of a green or yellowish-brown color with the formation of a Kaiser-Fleischer ring. The Kaiser-Fleischer ring is a specific symptom of hepatolenticular degeneration.

In the systemic blood stream the chemical element settles on the erythrocyte membrane, causing their death and the development of hemolytic anemia. The person reduces the number of red blood cells in the blood, jaundice, nosebleeds.

With kidney damage, tubular acidosis develops. It is manifested by the appearance in the urine of phosphates, urates, protein and glucose.

Postponing copper in other organs leads to fragility of bones, hyperpigmentation of the skin, damage to the heart, joints.

Diagnostic markers of the disease

In the patient's blood, an increased level of free and reduced-bound copper is determined.

Diagnostic tests reveal a number of characteristic signs of the disease:

1. Reduction of the concentration of bound Cu2 + and ceruloplasmin in the blood.
2. An increased concentration of free Cu2 + in the blood and urine.
3. Ring of the Kaiser-Fleischer.
4. The ultrasound of the internal organs confirms the presence of the disease.
5. MRI of the internal organs and the brain is performed to reveal the ailment.

Treatment

Medical measures are aimed at reducing the copper content in the body, maintaining the work of internal organs.

1. Diet (table no. 5a).

From the diet excluded products rich in copper (legumes, chocolate, liver, oatmeal, peanuts, cod).

1. Drug therapy.

• Used drugs that bind and remove Cu2 + from the body (D-penicillamine, Kuprenil, etc.).
• Hepatoprotectors (Essentiale N, Heptral, etc.) are used to protect hepatic cells from the toxic effects of copper.
• Antioxidants (Karsil, Legalon, etc.) normalize biochemical processes in internal organs.
• Symptomatic therapy of various complications from other organs and systems: treatment of anemia, endocrine disorders, mental disorders.

Forecast

With timely treatment begun, the disappearance of symptoms from the nervous system occurs six months later and persists for 2 years. Patients with Wilson-Konovalov's disease should take life-long medications that bind copper.

In the absence of treatment, severe disability of a person occurs, followed by a fatal outcome from hepatic and other complications.

Educational channel on neurology, lecture on "Wilson-Konovalov's Disease":

Wilson-Konovalov's disease

Watch this video on YouTube

On the illness of Wilson-Konovalov in the program "To live healthy!" With Elena Malysheva:

Disease Wilson - Konovalov. "Copper riot" of the body

Watch this video on YouTube