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The estimated prevalence at birth ranges between 1/30,000-110,000 worldwide but may be higher in isolated populations.

The clinical spectrum is very wide, even within affected families. Likewise, age of onset is highly variable. Some patients remain asymptomatic for decades while few present symptoms before age 3 to 5. The disease can be observed in children after 3 years and most cases develop by 40 years of age. Late-onset cases after the fifth decade of life have also been described. Clinical presentation depends on gender and age. In children, at an average age of 10 years, hepatic manifestations typically prevail, most often commencing with liver damage. In general, hepatic manifestations (hepatomegaly, subacute or chronic hepatitis, acute liver failure or cirrhosis with portal hypertension) commonly precedes neurologic symptoms. Neurological manifestations (dystonia, intention tremor, dysarthria, coordination difficulties, chorea, choreoathetosis, and gait disorders) can be found in conjunction with hepatic symptoms or might also be the first clinical symptoms. Isolated psychiatric disorders (depression, phobias, compulsive behavior, personality changes, aggressiveness, or emotional instability) are rare and more commonly observed in conjunction with hepatic or neurologic disease. A wide range of other manifestations may also be present in affected patients: acute hemolytic episodes, delayed puberty, amenorrhea, repetitive miscarriage, Kayser-Fleischer rings due to copper deposits in the Descemet membrane, bone pain, arthralgia and osteoporosis, arrythmia, myocardiopathy, hematuria, nephrotic syndrome and renal lithiasis. Hepatocellular carcinoma has been reported in rare cases.

The disease is due to chronic copper toxicosis, caused by pathogenic ATP7B (13q14.3) variants which leads to impaired copper elimination and subsequent accumulation in body tissues, particularly in the liver initially and then the brain and other organs.

The variable presentation (hepatic, neurologic, psychiatric) complicates diagnosis which is based primarily on the combination of clinical features, and abnormal laboratory tests (elevated liver enzymes, thrombocytopenia, low serum ceruloplasmin, elevated urinary copper excretion). Liver biopsy may be performed to demonstrate high copper levels. Evaluation of liver copper from biopsies can be helpful. Diagnostic scoring system is commonly applied to establish diagnosis, still the diagnostic approach should start with ceruloplasmin and urinary copper excretion evaluation. Molecular genetic testing most often confirms the diagnosis in 98% of cases. Family screening identifies 20% of cases.

For the liver presentation, the differential diagnosis includes acute or chronic hepatopathy (viral or autoimmune hepatitis, non-alcoholic steatohepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and alpha-1-antitrypsin); regarding the neurological presentation, it includes essential tremor, early onset Parkinson disease, and dystonia.

Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples if both individuals are carriers of a disease-causing mutation, informing them of the 25% risk of having an affected child at each pregnancy and the existence of an effective treatment.

There is currently no cure for Wilson disease. The main aim of current treatment is to establish a negative copper balance with the life-long administration of chelating agents (D-penicillamine, trientine salts) or zinc salt. Treatment helps to improve the manifestations of the disease over time, and its effectiveness depends on strict adherence to it throughout life. Restriction of copper-rich foods may be beneficial. Liver transplantation is the recommended therapy in cases of acute liver failure with encephalopathy or decompensated cirrhosis despite drug therapy.

The prognosis is dependent on timely diagnosis and initiation of treatment, and treatment compliance. If left untreated, the disease is progressive with a severe, life-threatening course but with the correct treatment, long-term prognosis is very good.