Wilson Disease

The prevalence of Wilson disease is usually reported as one in 30,000 in most populations. However, recent studies suggest genetic prevalence as high as one in 7,026. Prevalence may be greater in certain more isolated populations. Mismatch between clinical and genetic prevalence may be due to reduced penetrance and/or missed diagnoses.

Wilson disease results from absent or reduced function of the metal-transporting ATP7B protein, expressed mainly in hepatocytes, which leads to decreased hepatocellular excretion of copper into bile. The condition manifests as liver disease more commonly in children and younger adults; other major symptomology may include neurologic disease (e.g. movement disorders or rigid dystonia), mood disturbances, difficulty with motor skills, and psychiatric manifestations (e.g. depression, phobias, compulsive behaviors, aggression, or antisocial behavior). Kayser-Fleischer rings (deposits of copper in the cornea) are often present in patients with neurologic symptoms and may be found in those without neurologic symptoms but do not cause ocular difficulties. Clinical features of Wilson disease overlap with other liver diseases such as autoimmune liver diseases, and with neurologic symptoms characteristic of a variety of other neurologic disorders, resulting in potential for misdiagnosis. As a result, Wilson disease must be excluded in any patient with unexplained liver disease along with neurological or neuropsychiatric disorder.

Decreased copper excretion results in hepatic copper accumulation and injury, release of copper into the bloodstream, and copper deposition in other organs such as brain, kidneys, and cornea. After a presymptomatic period, approximately 40% of patients present acutely with liver failure, hemolytic anemia, or both, or more chronically with liver conditions such as chronic hepatitis, portal hypertension, or cirrhosis. In other patients, liver disease remains subclinical and neuropsychiatric symptoms develop, reflecting ongoing copper deposition in other organs. Clinically evident liver disease may precede neurologic manifestations by as much as 10 years, and most patients with neurologic symptoms have some degree of liver disease. However, neurological, behavioral, and/or psychiatric signs are present in almost 50% of patients at any one time, and present before motor signs in 20% of cases. Neuropsychiatric presentation can be extremely subtle, and intermitted for many years, but may also develop very rapidly, leading within a few months to complete disability. Wilson disease is uniformly fatal without treatment, with most patients dying from liver disease and a minority from complications of progressive neurologic disease. The majority of patients present between ages 5 and 35 but the oldest patients have been diagnosed in their early 70s. Symptoms at any age are frequently nonspecific and the spectrum of disease at presentation is highly variable.

1-2 in 5000

Unknown Unknown

Unknown

1. Is there a qualifying resource, such as a practice guideline or systematic review, for the genetic condition?
Yes
No
2. Does the practice guideline or systematic review indicate that the result is actionable in one or more of the following ways?
Yes
No

a. Patient Management

Yes
No

b. Surveillance or Screening

Yes
No

c. Circumstances to Avoid

Yes
No
3. Is there an intervention that is initiated during childhood (<18 years of age) in an undiagnosed child with the genetic condition?
Yes
No
4. Does the disease present outside of the neonatal period?
Yes
No
5. Is this condition an important health problem?
Yes
No
6. Is there at least on known pathogenic variant with at least moderate penetrance (≥40%) or moderate relative risk (≥2) in any population?
Yes
No
Unknown