Wilson’s disease is a hereditary disease transmitted by an autosomal recessive type. It occurs under conditions of mutations in the ATP7B gene encoding the copper-transporting liver ATPase protein. A characteristic feature of Wilson’s disease is the accumulation of copper in various organs and tissues, mostly in the liver and basal ganglia. Wilson’s disease can occur in abdominal, rigid-arrhythmohyperkinetic, tremulous or extrapyramidal-cortical form. Diagnosis of Wilson’s disease includes ophthalmological examination, biochemical urine and blood test, MRI or CT brain. The basis of pathogenetic therapy is thiol drugs, which can be taken for several years and even for life.
ICD 10
E83.0 Copper metabolism disorders
General information
Wilson’s disease is a hereditary disease transmitted by an autosomal recessive type. It occurs under conditions of mutations in the ATP7B gene encoding the copper-transporting ATP-aza protein of the liver. A characteristic feature of Wilson’s disease is the accumulation of copper in various organs and tissues, mostly in the liver and basal ganglia. The discoverer of the disease is A.K. Wilson, who described the disease in 1912, in domestic medicine — N.A. Konovalov. The pathogenesis of Wilson’s disease was identified in 1993. The concept of “Wilson’s disease” also corresponds to: Wilson-Konovalov disease, hepatocerebral dystrophy, hepatolenticular dystrophy, progressive lenticular degeneration.
Causes
The ATP7B gene is mapped on the long arm of chromosome 13 (13q14.3-q21.1). The human body contains about 50-100 mg of copper. The daily requirement of copper for humans is 1-2 mg. 95% of copper absorbed in the intestine is transported in the form of a complex with ceruloplasmin (one of the serum globulins synthesized by the liver) and only 5% in the form of a complex with albumin. In addition, the copper ion is part of the most important metabolic enzymes (lysyl oxidase, superoxide dismutase, cytochrome C oxidase, etc.). In Wilson’s disease, two processes of copper metabolism in the liver are disrupted — the biosynthesis of the main copper-binding protein (ceruloplasmin) and the excretion of copper with bile, resulting in an increase in the level of unbound copper in the blood. The concentration of copper in various organs (most often in the liver, kidneys, cornea and brain) increases, which leads to their toxic damage.
Classification
According to the classification of N.V. Konovalov, there are five forms of Wilson’s disease:
- abdominal
- rigid-arrhythmogyperkinetic
- tremor-rigid
- shaky
- extrapyramidal-cortical
Wilson’s disease symptoms
Wilson’s disease is characterized by clinical polymorphism. The first manifestations of the disease may appear in childhood, adolescence, adulthood and much less often in adulthood. In 40-50% of cases, Wilson’s disease manifests with liver damage, in the rest — with mental and neurological disorders. With the involvement of the nervous system in the pathological process, the Kaiser-Fleischer ring is detected.
The abdominal form develops mainly up to 40 years. A characteristic feature is severe liver damage by the type of cirrhosis of the liver, chronic hepatitis, fulminant hepatitis.
The rigid-arrhythmogyperkinetic form manifests in childhood. Initial manifestations are muscle rigidity, amymia, blurred speech, difficulty performing small movements, moderate decrease in intelligence. This form of the disease is characterized by a progressive course, with the presence of episodes of exacerbation and remission.
The tremulous form occurs at the age of 10 to 30 years. The predominant symptom is tremor. In addition, there may be bradykinesia, bradylalia, severe psycho-organic syndrome, epileptic seizures.
The extrapyramidal-cortical form is very rare. Its beginning is similar to the beginning of any of the above forms. It is characterized by epileptic seizures, extrapyramidal and pyramidal disorders and pronounced intellectual deficits.
Diagnostics
An ophthalmological examination using a slit lamp reveals the Kaiser-Fleischer ring. Biochemical studies of urine reveal an increased excretion of copper in the daily urine, as well as a decrease in the concentration of ceruloplasmin in the blood. With the help of imaging methods (CT and MRI of the brain), atrophy of the hemispheres of the cerebrum and cerebellum, as well as basal nuclei, is detected.
When diagnosing Wilson’s disease, a neurologist needs to differentiate it from Parkinsonism, hepatocerebral syndrome, Gellervorden-Spatz disease. The main differential diagnostic feature of these diseases is the absence of Kaiser-Fleischer rings characteristic of Wilson’s disease and copper metabolism disorders. Gene diagnostics is performed to confirm Wilson’s disease.
Treatment
The basis of pathogenetic treatment is the appointment of thiol drugs, primarily D-penicillamine or unithiol. The main advantage of kuprenil is low toxicity and the possibility of long—term use in the absence of side effects. It is prescribed for 0.15 g (1 capsule) per day (only after meals), in the future, for 2.5-3 months, the dose is increased to 6-10 capsules / day (the optimal dose). Treatment with D-penicillamine is carried out for years and even for life with short breaks (for 2-3 weeks) in case of side effects (thrombocytopenia, leukopenia, exacerbation of gastric ulcer, etc.).
Unithiol is prescribed in case of intolerance (poor tolerance) of D-penicillamine. The duration of one course of treatment is 1 month, after which treatment is suspended for 2.5-3 months. In most cases, there is an improvement in the general condition of the patient, as well as a regression of neurological symptoms (stiffness, hyperkinesis). In the case of hyperkinesis dominance, the appointment of small courses of neuroleptics is recommended, with rigidity — levodopa, carbidopa, trihexyphenidyl.
In the case of severe Wilson’s disease, with the ineffectiveness of conservative treatment abroad, liver transplantation is resorted to. With a positive outcome of the operation, the patient’s condition improves, the exchange of copper in the body is restored. Further treatment of the patient is immunosuppressive therapy. In Russia today, the method of biohemoperfusion with isolated living cells of the spleen and liver (the so-called “auxiliary liver” device) is gradually being introduced into clinical practice. Non-drug treatment consists in prescribing a diet (table No. 5) in order to exclude products rich in copper (coffee, chocolate, legumes, nuts, etc.).
Prognosis and prevention
In case of timely diagnosis of Wilson’s disease and adequate copper-lowering therapy, normalization of the patient’s general condition and copper metabolism in the body is possible. The constant intake of thiol drugs according to the scheme prescribed by a specialist doctor allows you to maintain the professional and social activity of the patient.
To prevent relapses of Wilson’s disease, it is recommended to conduct laboratory tests of the patient’s blood and urine several times a year. It is necessary to monitor the following indicators: the concentration of copper, ceruloplasmin and zinc. In addition, it is recommended to conduct a biochemical blood test, a general blood test, as well as regular consultations with a therapist and a neurologist.
