Clinical Guidance

No genotype-phenotype correlations for ATP7B have been identified .

Source: GeneReviews — "Wilson Disease"

Diagnostic Criteria

The diagnostic algorithm for Wilson disease in the European Association for Study of Liver (EASL) Clinical Practice Guidelines is based on a diagnostic index ("Leipzig" score) proposed by an expert panel . This score includes clinical, biochemical, and molecular findings, but has not been validated in large patient series. The most recent diagnostic pathway of the American Association for Study of the Liver Diseases (AASLD) highlights diagnostic approaches when clinical and biochemical evaluations are ambiguous .

Suggestive Findings

Wilson disease should be suspected in individuals ages three to 45 years, but age alone should not exclude consideration of the diagnosis, as affected individuals have been diagnosed in their early 70s.

Source: GeneReviews — "Wilson Disease"

Differential Diagnosis

The complete differential diagnosis of Wilson disease is extensive and includes: • Copper metabolism disorders; • Hereditary disorders involving the liver; • Hereditary disorders involving the nervous system; and • Acquired conditions such as viral hepatitis, severe drug toxicity, and nonalcoholic steatohepatitis (NASH). Note: Wilson disease must be specifically excluded in individuals thought to have NASH, or the opportunity for life-saving treatment will be missed. lists selected genetic disorders of interest in the differential diagnosis of Wilson disease (see also , Table 5). Table 4. Hereditary Disorders of Known Genetic Cause in the Differential Diagnosis of Wilson Disease

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual with symptomatic untreated Wilson disease, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with Symptomatic Untreated Wilson Disease

Clinical Guidance

Foods very high in copper (liver, brain, chocolate, mushrooms, shellfish, and nuts) should be avoided, especially at the beginning of treatment. In case of biochemical abnormalities in liver function tests or transaminases, alcohol consumption is strongly discouraged.

Source: GeneReviews — "Wilson Disease"

Therapies Under Investigation

Tetrathiomolybdate (TTM) is an orally administered chelating agent proposed to work by multiple mechanisms including:

• Detoxifying non-ceruloplasmin-bound copper by creating a nonreactive tripartite complex with albumin and copper;

• Extracting copper from the endogenous cellular chelator metallothionein (based on its high affinity for copper); and

• Interfering with the intestinal uptake of copper when administered with food.

Source: GeneReviews — "Wilson Disease"

Surveillance Guidelines

Assessment of Treatment Effectiveness and Adherence to Medical Interventions to Prevent/Treat Copper Accumulation Monitoring of individuals under therapy should include routine assessments of treatment efficacy by biochemical testing and clinical evaluation.

• Insufficient therapy, underdosage, or poor adherence could lead to reaccumulation of copper and development of new symptoms.

• Adverse events related to medical treatment (especially under D-penicillamine treatment) should be evaluated.

• Excessive long-term treatment could result in copper deficiency, leading to immobilization of iron (as observed in aceruloplasminemia) and neurologic symptoms of copper deficiency .

According to current guidelines (AASLD and EASL Clinical Practice Guidelines ), routine monitoring should include the following examinations:

• At least twice annually: serum copper and ceruloplasmin, liver biochemistries, international normalized ratio, complete blood count, urinalysis, and physical examination including neurologic assessment

Note: Individuals receiving chelation therapy require a complete blood count and urinalysis regularly, no matter how long they have been on treatment.

• At least once annually: 24-hour urinary excretion of copper

Note: Measurements are recommended more frequently if there are questions on adherence or if dosage of medications is adjusted.

Supportive Care

To monitor the individual's response to supportive care and the emergence of new manifestations, the evaluations in are recommended b...

Source: GeneReviews — "Wilson Disease"