Often fatal if untreated (due to progressive cirrhosis and neurodegeneration). Early recognition allows chelation therapy to prevent irreversible hepatic and neurologic damage.
Hepatic presentation (most common): typically in adolescence with signs of chronic liver disease (hepatitis → cirrhosis). Can present as acute liver failure (fulminant hepatitis with coagulopathy), often accompanied by Coombs-negative hemolytic anemia.
Neuropsychiatric presentation: usually young adults with movement disorders (tremor, dystonia, parkinsonian features) and personality or mood changes (depression, irritability). Kayser-Fleischer rings (brown copper deposits at the corneal limbus) are often present on slit-lamp exam when neurologic symptoms occur.
Maintain a high index of suspicion in any young patient with unexplained liver disease or atypical movement/psychiatric disorder — Wilson disease is treatable and often missed.
Screen with ceruloplasmin level (low <20 mg/dL in ~90% of cases, though can be normal in inflammation or rare cases). If low (or clinical suspicion remains high), proceed with confirmatory tests.
Confirm the diagnosis with a 24-hour urine copper (elevated copper excretion) and slit-lamp exam for Kayser-Fleischer rings; if needed, perform liver biopsy for quantitative copper or genetic testing for *ATP7B* mutations.
Recognize that other conditions can also lower ceruloplasmin (e.g. protein-losing states, malnutrition) — interpret labs in context. In acute liver failure, a very low alkaline phosphatase with high AST and hemolysis strongly suggests Wilson disease.
Start copper chelation therapy as soon as Wilson disease is diagnosed; do not delay treatment, as ongoing copper accumulation leads to permanent organ damage. Also screen first-degree relatives for Wilson disease.
hereditary iron overload; cirrhosis with diabetes & skin pigmentation; typically older onset
Huntington disease
autosomal dominant neurodegeneration (chorea, dementia) with family history; no liver involvement
Lifelong copper removal: chelators like D-penicillamine (first-line) or trientine to bind and excrete copper; plus high-dose zinc to block copper absorption and a low-copper diet (avoid organ meats, shellfish, nuts, chocolate).
Liver transplant for fulminant Wilson disease or end-stage cirrhosis (curative by restoring normal copper excretion).
Penicillamine can be remembered as a 'penny' (copper coin) – it's the first-line chelator to treat copper overload.
Fulminant Wilson disease – acute liver failure with rapid hemolysis in a young patient – is an emergency; without transplant it has a high fatality. Always consider Wilson disease in any unexplained acute hepatic failure in a teenager.
Non-adherence or stopping chelation can lead to re-accumulation of copper and sudden neurologic deterioration. Emphasize strict lifelong therapy to prevent irreversible damage.
Young patient with unexplained liver dysfunction or neuropsychiatric symptoms → suspect Wilson disease.
Initial tests: check serum ceruloplasmin (low in most cases) and liver enzymes; also examine eyes (slit lamp) for Kayser-Fleischer rings.
If ceruloplasmin is low (or high suspicion persists): confirm with 24h urinary copper (elevated) and/or liver biopsy for copper; perform *ATP7B* genetic testing to solidify diagnosis and for family screening.
Begin chelation therapy (e.g. D-penicillamine) promptly upon diagnosis; add zinc to reduce dietary copper uptake. Avoid high-copper foods.
If patient develops acute liver failure or has decompensated cirrhosis despite therapy → refer for liver transplantation (definitive cure).
Teenager with jaundice, asterixis, and acute liver failure (↑AST/ALT into 1000s) plus Coombs–negative hemolytic anemia; slit-lamp shows corneal deposits (Kayser-Fleischer rings) → Wilson disease.
Young adult with a resting tremor, dysarthria, personality changes, and mildly ↑LFTs; slit-lamp exam reveals Kayser-Fleischer rings in the cornea → Wilson disease.
Case 1
A 16‑year‑old boy presents with jaundice, abdominal distension, and confusion. He has ascites and a flapping tremor at the wrist (asterixis).
Case 2
A 23‑year‑old man is evaluated for tremors and behavioral changes. Over a year, he developed slurred speech, difficulty with handwriting, and depression.
Kayser-Fleischer ring in the eye of a Wilson disease patient (brown copper deposit at corneal edge).
