hepatolenticular disease

August 12, 2017 17:51 | Genetic Diseases

gepatotserebralnoy degeneration (Wilson's disease) - a disease that develops as a result of excess accumulation in the body and the toxic effects of copper.This pathology is characterized by the combined lesions of the internal organs, especially the liver and brain.Dispatched Wilson's disease is an autosomal recessive inheritance type.

The frequency of Wilson's disease in the population is 1-W cases per 100 000 population.The disease has an uneven geographical and ethnic distribution.It occurs more frequently in Japan, Italy, India.

The disease is caused by mutations in the 13th chromosome.Due to a genetic defect disrupts the functioning of the system, carrying out transport copper in the liver cells and excretion of excess copper in the bile, and its inclusion in the ceruloplasmin protein molecule.This increases the concentration of "free" (non-ceruloplasmin) copper in the blood, its accumulation in various tissues and organs, especially the liver, brain, kidneys, organ of vision, erythrocytes, to th

e development of chronic intoxication copper.

in liver cells appear dystrophic and necrotic changes, formed chronic hepatitis (steatosis), followed by the transition to cirrhosis.Dystrophic changes in the kidney and developed.In the brain, nerve cell damage occurs and blood vessels.Defeat of small vessels and capillaries of the brain leads to insufficient oxygen supply to the brain tissue and nutrients (ischemia) and destruction (necrosis) with the formation of multiple small cysts (round shape of the cavity filled with inflammatory fluid) of the brain and wrinkled.

first symptoms appear 1-3 decade of life.

In the course of the disease there are three main stages.

presymptomatic stage. At this stage there are no symptoms of the disease, however, for special laboratory studies determined characteristic metabolic disorders.The most reliable and accurate method to identify genetic mutations in the presymptomatic stage is molecular genetic testing.Identification of individuals homozygous for the mutant gene, it is necessary first of all among the close relatives of a famous person and a patient is carried out for prophylactic treatment to prevent the disease.Such measures are referred to as secondary or post-natal prevention.

visceral (or prenevrologicheskaya) stage. Symptoms specific to this stage, for the first time appear in the 1 - 2 decades of life.Their appearance is associated with a variety of disorders of the internal organs.Excessive accumulation of copper in the liver leads to the development of chronic hepatitis (gepatoza) and cirrhosis.The defeat of the red blood cells leads to their destruction and the excessive development of anemia.Such changes in the blood are more frequent in children.Renal disease can manifest itself in the form of appearance of blood impurities, the appearance of an excess amount of protein, white blood cells, can also be marked decrease or increase in the number of daily urine.Ultimately, all of these changes come to an end the development of chronic renal failure.The defeat of the heart and joints is expressed by the appearance of pain.Also undergoes pathological changes and the endocrine system, which is manifested hypoplasia of the genital organs and glands in women stops menstruating.Disorders of internal organs do not have any specific symptoms, and therefore the Wilson's disease at this stage, as a rule, remains unrecognized.Hepatitis may occur acutely in the guise of infectious hepatitis, but more often develops hidden until the formation of liver cirrhosis and its complications (portal hypertension, splenomegaly, hepatic coma).This occurs without jaundice, hepatitis, and characteristic laboratory signs.However, in this case it is determined by the low level of protein ceruloplasmin, which does not occur in hepatitis and cirrhosis of other origin.Sometimes hepatitis in childhood and juvenile (youth) age becomes a lightning (fulminant) for the rapid development of liver failure and death.One variant of the Wilson's disease, which occurs with primary liver disease, attributed to NV Konovalov abdominal ( "abdominal") form.As a result, abnormal liver function decreased formation in it of substances that promote blood clotting.As a result of pathologic changes occur in the blood, accompanied by increased permeability of the capillaries and leads to the formation of a hemorrhagic syndrome.Hemorrhagic syndrome is characterized by increased bleeding gums, frequent nosebleeds, groundless (spontaneous) formation of multiple bruising.

Neurological stage characterized by the fact that, on the foreground of the nervous system disorder (brain) as a combination of 3 main symptom:

1) extrapyramidal symptom is presented in two different versions:

a) akinetic-rigid syndrome is characterized by an increase in volumeand the number of involuntary movements that are irregularly;and the syndrome can manifest trembling limbs (tremor);

b) common pattern of major shake (on a background of reduced or unchanged in muscle tone).Jitter is more pronounced in the hands and resembles a "bird's wings flapping," can grow in any attempt of active movement to the extent of the motor storm;

2) pseudobulbar syndrome disorder manifested voice, speech, swallowing, appearance on the face of violent involuntary smile or cry;

3) psycho-organic syndrome with intellectual disorder, memory, speech, thought, a violation of the emotional sphere and behavior.In addition, it can be marked psychotic episodes.

According NV Konovalov, there are the following forms of the disease:

1) rigid-aritmogiperkineticheskaya (first manifestations occur in 7-15 years);

2) rigid-trembling (the first manifestations occur in 15-25 years);

3), tremor (the first manifestations occur in 20-25 years later);

4), extrapyramidal cortical (may develop in any of the forms of the disease when acceding to the paralysis of one half of the body, seizures and rapidly progressing mental disorders).

diagnosis of Wilson's disease is fully confirmed in the case of the presence of a person following characteristic features:

1) autosomal recessive transmission of the disease, which is determined during the family study in genetic centers;

2) the appearance of the first signs of the disease in the 1-3 decade of life;

3) the simultaneous defeat of many organs and systems;

4) the appearance of signs of chronic hepatitis B (gepatoza) and liver cirrhosis;

5), extrapyramidal disorders (increase in volume and the number of involuntary movements that are spasmodic, common pattern of major shake against a background of reduced or unchanged in muscle tone) in combination with mental disorders;

6) reduction of content in the blood protein ceruloplasmin, urinary excretion of large amounts of copper, increasing the concentration of copper in the liver tissue (as determined by biopsy, ie taking a lifetime piece of body tissue followed his research)..;

7) continuously progressive course of the disease;

8) positive results in DNA research.

treatment. Throughout a person's life suffering from Wilson's disease, treatment with drugs should be carried out, leading out the copper from the body.The main drug to such an action is a D-penicillamine (kuprenil, metallkaptaza, artamin et al.).Treatment starts with receiving capsule 1 (0.15 or 0.25 grams) daily or every other day, gradually increasing doses every 1-2 weeks for one capsule.Such an increase in dose should be carried out to achieve a daily intake of 1-1.5 g Subsequently, after 1-2 years, transferred to maintenance treatment.This daily dose of the drug should be 0,45-1 In 1982 for the treatment of Wilson's disease less toxic drug has been proposed that outputs copper from the body - trientine.The recommended dose for the treatment of this disease is 400-800 mg 3 times a day.Tetrathiomolybdate is a promising new agent.Preparations zinc (zinc sulfate, zinc acetate) administered every 4 hours between meals and at bedtime.These drugs reduce the absorption of copper, are somewhat weaker and slower but have lower toxicity and recommended in the initial stages of the disease and for preventive treatment in the early stages of the disease.People with Wilson's disease need to follow a diet, gentle liver.This diet should exclude foods rich in copper (beans, mushrooms, nuts, chocolate, biscuits, shrimp).In addition, a prerequisite for achieving positive results is the regular course of vitamin therapy.This should be used in the B vitamins, especially B6, vitamin E, ascorbic acid.Good effect has essentiale drug.In severe illness with symptoms of liver failure is performed a liver transplant.