Wilson-Konovalov disease
Last reviewed: 23.04.2024
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Wilson-Konovalov's disease (hepatolenticular degeneration) is a rare hereditary disease of a predominantly young age that is caused by a disruption in the biosynthesis of ceruloplasmin and copper transport, leading to an increase in copper content in tissues and organs, especially in the liver and brain and characterized by cirrhosis, bilateral softening and degeneration of the basal nuclei of the brain, the appearance of greenish-brown pigmentation along the periphery of the cornea ( Kaiser-Fleischer ring ).
The disease was first described by SA Kinnier Wilson in 1912 as "a specific symptom complex, the main manifestations of which are generalized tremor, dysarthria and dysphagia, muscle rigidity and hypertonia, exhaustion, spastic contractions, contractures, increased emotionality. Mental symptoms can be transient and resemble the manifestations of toxic psychosis, but they are not so severe and more chronic, they include the general narrowing of the mental horizon, some absent-mindedness or obedience without delirium or hallucinations. They do not necessarily progress to the same extent as neurological symptoms. In some cases of illness, mental symptoms are very easy or absent "(Wilson, 1912). Although Wilson described the majority of clinical manifestations of the disease, he did not pay attention to liver damage and pathological pigmentation of the cornea. The latter develops due to the deposition of copper in the cornea and is designated as the Kaiser-Fleischer ring.
Causes of Wilson-Konovalov's disease
Hepatolenticular degeneration is a hereditary disease and is transmitted by an autosomal recessive type.
The disease occurs with a frequency of 1:30 000 people. The abnormal gene responsible for the development of the disease is localized in the region of the XIII chromosome. Each patient is a homozygous carrier of this gene. The disease is spread all over the world, but is more common among Jews of Eastern European origin, Arabs, Italians, Japanese, Chinese, Indians and in populations where closely related marriages are frequent.
Hepatolenticular degeneration is caused by a mutation of the copper transfer gene located on the 13th chromosome. The disease usually manifests itself in the 2-3rd decades of life mainly by neurological and mental symptoms or symptoms associated with liver damage (each of these symptom groups prevails in a third of cases). Sometimes the symptoms appear in the first decade of life, very rarely - in the sixth.
Causes of Wilson-Konovalov's disease
[Pathogenesis of Wilson-Konovalov's disease
With hepatolenticular degeneration, there is a genetic defect in the synthesis of ceruloplasmin (copper-oxidase) in the liver, related to a2-globulins. The meaning of ceruloplasmin lies in the fact that it keeps copper in the blood in a bound state. With food, the body receives about 2-3 mg of copper per day in the intestine, about half of this amount is absorbed, enters the blood, binds to ceruloplasmin, is delivered to the tissues and is incorporated into specific apoenzymes.
Symptoms of Wilson-Konovalov's disease
The clinical picture is characterized by a variety that is caused by the damaging effect of copper on many tissues. The primary lesion of an organ depends on the age. At children it basically a liver (hepatic forms). In the future, begin to prevail neurological symptoms and mental disorders (neuropsychiatric forms). If the disease manifests itself after 20 years, then patients usually have neurological symptoms. Perhaps a combination of symptoms of both forms. The majority of patients aged 5 to 30 years have already expressed clinical manifestations of the disease or a diagnosis.
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Diagnosis of Wilson-Konovalov's disease
The levels of ceruloplasmin and copper in the serum are usually reduced. Differential diagnosis is carried out with acute and chronic hepatitis, in which the level of ceruloplasmin can be reduced due to a violation of its synthesis in the liver. Malnutrition also reduces the level of ceruloplasmin. When taking estrogens, oral contraceptives, with obstruction of the biliary tract, during pregnancy, the level of ceruloplasmin may increase.
Treatment of Wilson-Konovalov's disease
The drug of choice is penicillamine. It binds copper and increases its daily excretion in urine to 1000-3000 μg. Treatment begins with the appointment of penicillamine hydrochloride at a dose of 1.5 g / day in 4 meals before meals. Improvement develops slowly; It takes at least 6 months of continuous intake of the drug at this dose. If there is no improvement, the dose can be increased to 2 g / day. In 25% of patients with central nervous system damage, the condition can first worsen and only then there are signs of improvement. The Kaiser-Fleischer ring decreases or disappears. Speech becomes more clear, tremor and stiffness decrease. The mental status is normalized.
Forecast
Without treatment, Wilson's disease progresses and leads to the death of patients. The most dangerous situation is when the disease remains unrecognized and the patient dies without receiving treatment.