Diagnostics of Wilson's disease - analysis of the most common mutation p.His1069Arg of the ATP7B gene and other mutations in exon 8

Diagnosis of Wilson's disease - analysis of the most common p.His1069Arg mutation of the ATP7B gene and other mutations in exon 8

Clinical significance

Wilson's disease is a rare disorder of copper metabolism, with an estimated incidence of just over 1:30,000 peopleób. It is caused by a disruption of membrane ionów transport caused by impaired function of the intracellular transporter, Cu2+-transporting polypeptide beta ATPase, leading to the formation of unstable ceruloplasmin and progressive deposition of copper in tissues. Wilson's disease is caused by mutations in the ATP7B gene on chromosome 13q14. Several recurrent mutations are observed, correlating significantly with the clinical course. Recessive inheritance. Wilson's disease follows a hepatic course in about 40% of cases, with onset of symptomsóin early childhood or adolescence (6-15 years of age). Symptoms can range from mild liver enlargement with moderate elevated liver enzymesóto progressive chronic hepatitis with failure and jaundice, coagulation abnormalities and abdominal fluid accompanied by hypoalbuminemia. In ogó³ the earlier the onset, the more severe the symptoms, sometimes there is acute liver failure. Another 40% of cases are neurological, with onset of symptoms in adulthood (20-40 years of age), typical of Slavic countries. Motor symptoms predominate, initially with difficulties in speaking, chewing and swallowing, which are joined by tremors, loss of precision of movementów (balance, writing), and then spastic dystonia (mask-like face, stiffness, gait disturbance). It is accompanied by symptoms of liver damage, usually of low intensity. The third psychiatric form accounts for about 20% of cases of Wilson's disease, with onset in póeature. Initially, there are difficulties in focusing attention and doing previous work, impulsivity, obsessive and neurotic behavior (including phobias), depression; as the disease progresses, there is personality disorganization (anxiety, affect changes, mood lability, disinhibitions) and intellectual regression (memory impairment, difficulty in abstract thinking). Patients are also found to have neurological symptoms, usually mildly severe. Characteristic in all forms are Kayser's and Fleischer's ring in the hornówings (hepatic form in 50%, neurological and psychiatric forms in 90% of patients), low levels of ceruloplasmin in the blood increased excretion of copper in the urine. There are also symptoms of damage to other organsów including the kidneys, muscles and heart, pancreas, jointsów, as well as intermittent fever and excessive skin pigmentation. In the absence of treatment, survival is significantly shortenedócon. Indications for the test are: - diagnosis of cases of chronic liver disease with onset in childhood or adolescence, especially leading to liver failure accompanied by low blood ceruloplasmin levels or high urinary copper levels;- diagnosis of cases of;in progressive neurological disease with onset in early adulthood, especially with marked movement disorders, spastic dystonia and pseudobulbar palsy, or accompanying liver damage or copper disorders (low blood ceruloplasmin level, high urinary copper level);- diagnosis of cases of progressive psychiatric illness with gradual changes in personality and intellectual regression, especially with associated copper metabolism disorders (low blood ceruloplasmin level, high urinary copper level);- family studies: detection of ATP7B gene mutation in a relative with symptoms of liver damage, central nervous system or mental illness, especially in asymptomatic siblings with low ceruloplasmin levels, there is a possibility of prenatal testing.

Patient preparation

no special recommendations

Material: EDTA blood

Interventions

none