✅ Model Answer:
• Diagnosis: Wilson disease — autosomal recessive copper accumulation disorder (ATP7B gene). Progressive ataxia, dysarthria (slurred speech), abnormal movements (dystonia, tremor, chorea), and behavioral changes. Low ceruloplasmin (10 mg/dL), elevated 24-hour urinary copper (120 μg/24h), and mildly elevated liver enzymes.
• Any other test: Slit-lamp examination for Kayser-Fleischer rings (copper deposition in Descemet's membrane), 24h Urinary Copper, MRI Brain (basal ganglia T2 hyperintensities — putamen, caudate, thalamus), genetic testing for ATP7B mutations, liver biopsy (if diagnosis uncertain), serum free copper, 24-hour urinary copper (already done).
• What to do next: Start copper chelation therapy (trientine or D-penicillamine) OR zinc acetate (if asymptomatic or maintenance). Low copper diet. Monitor urinary copper and neurologic status.
• Follow-up plan: Lifelong treatment. Monitor liver function, neurologic exam, serum ceruloplasmin/24h copper. Genetic counseling for siblings. Liver transplant if fulminant liver failure or end-stage liver disease.

✅ Model Answer:
• Wilson disease (WD) is an autosomal recessive disorder of copper metabolism leading to copper accumulation in the liver, brain, cornea, and kidneys.
• Gene: ATP7B gene located on chromosome 13q14.3.
• Protein: ATP7B (copper-transporting ATPase) — transports copper into the Golgi apparatus for excretion into bile and incorporation into ceruloplasmin.
• Mutations: Over 500 mutations identified (mostly missense, nonsense, deletions).
• Inheritance: Autosomal recessive (both parents are carriers).
• Prevalence: 1 in 30,000 individuals; carrier frequency 1 in 90.
• Pathophysiology: Copper accumulation → oxidative stress → tissue damage (liver, brain, cornea, kidneys).

✅ Model Answer:
• Clinical features:
- Hepatic: Acute hepatitis, chronic hepatitis, cirrhosis, fulminant liver failure, hepatosplenomegaly, jaundice, elevated transaminases.
- Neurologic: Progressive ataxia, dysarthria (slurred speech), dystonia, tremor (wing-beating tremor), chorea, parkinsonism, gait disturbance, abnormal movements, rigidity.
- Psychiatric: Behavioral changes, depression, anxiety, personality changes, psychosis, cognitive decline, irritability.
- Ocular: Kayser-Fleischer rings (copper deposition in Descemet's membrane) — pathognomonic (seen in 95% of neurologic cases).
- Renal: Fanconi syndrome (proximal renal tubular acidosis), aminoaciduria, glycosuria, hypercalciuria, nephrolithiasis.
- Other: Hemolytic anemia (Coombs-negative), arthritis, cardiomyopathy (rare).

✅ Model Answer:
• Gold standard: Combination of clinical features + lab findings.
• Laboratory tests:
- Ceruloplasmin: Low (<20 mg/dL) — normal 20-40 mg/dL.
- 24-hour urinary copper: >100 μg/24h (normal <40 μg/24h).
- Serum free copper: >25 mcg/dL (normal <15 mcg/dL).
- Serum copper: Low (total copper).
- AST/ALT: Mildly elevated (hepatic involvement).
- Hemoglobin: May be low (hemolytic anemia).
• Slit-lamp examination: Kayser-Fleischer rings (copper deposition in cornea).
• MRI Brain: T2 hyperintensities in basal ganglia (putamen, caudate, thalamus), brainstem, cerebellum.
• Genetic testing: ATP7B gene mutations (confirmatory).
• Liver biopsy: Hepatic copper >250 μg/g dry weight (normal <50 μg/g).
• D-Penicillamine challenge: Urinary copper >1600 μg/24h after 500 mg D-penicillamine (diagnostic).

✅ Model Answer:
• Kayser-Fleischer (KF) rings: Golden-brown or greenish rings at the limbus of the cornea (Descemet's membrane).
• Pathophysiology: Copper deposition in the cornea due to excess circulating free copper.
• Detection: Seen on slit-lamp examination (not visible to the naked eye).
• Diagnostic significance:
- Pathognomonic for Wilson disease (present in 95% of neurologic cases, 50% of hepatic cases).
- Absence of KF rings does NOT exclude Wilson disease (especially in hepatic presentation).
- Presence of KF rings + low ceruloplasmin + high urinary copper = Wilson disease.
• Prognostic: KF rings may fade with effective chelation therapy.
• Other causes: Rarely seen in other cholestatic liver diseases (e.g., primary biliary cirrhosis).

✅ Model Answer:
• Medical therapy (lifelong):
- Copper chelation:
• D-penicillamine: 250-500 mg/day (first-line, but has side effects: nephrotoxicity, myelosuppression, lupus-like syndrome).
• Trientine (triethylenetetramine): 1-2 g/day (better tolerated than penicillamine).
- Zinc acetate: 25-50 mg TID (induces metallothionein, blocks copper absorption). Used for asymptomatic patients or maintenance therapy.
- Dietary modification: Low copper diet (avoid shellfish, nuts, chocolate, liver, mushrooms).
- Vitamin B6 (pyridoxine): Supplement if on D-penicillamine.
• Liver transplantation:
- Indicated for fulminant liver failure or end-stage liver disease.
- Curative (replaces the defective ATP7B liver enzyme).
• Neurologic: Parkinsonism may improve with copper chelation; consider symptomatic treatment (anticholinergics, benzodiazepines).
• Psychiatric: Psychiatric evaluation and treatment as needed.

✅ Model Answer:
• Complications:
- Liver: Cirrhosis, portal hypertension, liver failure, hepatocellular carcinoma (rare).
- Neurologic: Permanent neurologic damage (dystonia, ataxia, tremor, cognitive decline) — may be irreversible if treatment is delayed.
- Psychiatric: Behavioral changes, psychosis, depression, suicide risk.
- Renal: Fanconi syndrome, nephrolithiasis, renal failure.
- Hematologic: Hemolytic anemia (Coombs-negative), thrombocytopenia (hypersplenism).
- Ocular: Kayser-Fleischer rings (may persist despite treatment).
- Bone: Osteoporosis, osteomalacia, arthritis.
- Cardiac: Cardiomyopathy (rare).
- Death: From liver failure, complications of cirrhosis, or suicide.

✅ Model Answer:
• Prognosis:
- Good: With early diagnosis and lifelong treatment (copper chelation or zinc).
- If untreated: Progressive liver failure and neurologic deterioration → death by 30s.
- Liver transplantation: Curative (90% survival at 5 years).
- Neurologic: Symptoms may improve with treatment, but some deficits may be permanent if treatment is delayed.
- Psychiatric: May improve with copper reduction, but may require ongoing psychiatric support.
• Long-term follow-up:
- Monitor: Liver function tests, ceruloplasmin, 24-hour urinary copper, neurologic exam, psychiatric evaluation.
- Genetic counseling: Autosomal recessive (25% recurrence risk for siblings).
- Siblings: Screen siblings (ceruloplasmin, 24h urinary copper, genetic testing).
- Pregnancy: Continue treatment; adjust D-penicillamine dose (teratogenic).
- Compliance: Lifelong adherence to treatment is essential to prevent relapse.