Last updated: October 31, 2014
Synonyms: Hepatolenticular degeneration.
ICD-9 Code: 275.1
ICD-10 Code: E83.0
Definition: Wilson’s disease is an autosomal recessive genetic multisystem disorder caused by excess copper accumulation, particularly in the brain and liver. The disease is caused by mutations in the ATP7B gene; this gene encodes an enzyme affecting copper transport and incorporation into ceruloplasmin.
Demographics: This unusual multisystem disorder is transmitted in an autosomal recessive manner; it has an estimated prevalence of one in 30,000 to 50,000 with a carrier rate of 1/100 for abnormalities in the ATP7B gene. Although manifestations, particularly related to liver dysfunction, often become apparent in childhood, a number of cases are not detected until after adolescence.
Cardinal Findings: Deposition of excess copper can be observed in the cornea as the characteristic Kayser-Fleischer rings. Common presenting symptoms include those of a movement disorder (from basal ganglia deposition) as well asother neurologic (seizure, migraine) and psychiatric (depression, psychosis, anxiety) symptoms. Evidence of liver dysfunction can include jaundice, bleeding diathesis, and signs and symptoms or portal hypertension or ultimately liver failure.
Musculoskeletal manifestations seen in <50% adults (rare in children), and manifest most commonly as premature OA with a polyarthropathy involving wrists, metacarpophalangeal joints, knees, and spine. Knee effusions may be seen with associated chondromalacia patellae or chondrocalcinosis. Significant osteoporosis is present in approximately one-half of all patients. Joint abnormalities are generally not as severe as those seen in hemochromatosis. Renal tubular acidosis and cardiomyopathy can also be seen.
Diagnostic Tests: Increased copper deposition on liver biopsy is diagnostic. Low serum levels of ceruloplasmin are consistent with the diagnosis, being found in approximately 90% of patients (however, ceruloplamin can function as an acute phase reactant, and levels may increase with systemic inflammation). Urinary copper excretion can be diagnostic or supportive of the diagnosis. Analysis for genetic mutations can be performed, and a number of patients have been identified after a family member became symptomatic.
Imaging: Radiographic findings include joint space loss, marked osteophytes, subchondral cysts, and chondrocalcinosis.
Keys to Diagnosis: Suspect this diagnosis in any patient younger than 40 years old with persistent, unexplained liver abnormalities and neuropsychiatric symptoms.
Therapy: The aim of treatment for Wilson’s disease is to lower copper concentrations. Dietary manipulation may be of benefit. Initial therapy often consists of chelating agents, such as penicillamine and trientine HCL. Zinc supplementation can help lower intestinal copper transport. In severe cases, liver transplantation may be required.
Weiss KH, Stremmel W. Clinical considerations for an effective medical therapy in Wilson's disease. Ann N Y Acad Sci. 2014;1315:81-5. doi: 10.1111/nyas.12437. PMID: 24754532
Merle U, Schaefer M, Ferenci P, Stremmel W (2007). "Clinical presentation, diagnosis and long‐term outcome of Wilson's disease: a cohort study". Gut 56 (1): 115–20. PMID 16709660.