Wilson's Disease
Gastroenterology
Illness script · Gastroenterology
Wilson's Disease
Autosomal recessive ATP7B mutation causing defective hepatic copper excretion, leading to toxic copper accumulation in liver, brain, and eyes.
This illness script for Wilson's Disease covers predisposing factors, classic presentation, mechanism, workup, management, and the clinical pivots that separate it from look-alikes—written for USMLE Step 1 and clerkship reasoning.
01
Predisposing factors
- Autosomal recessive; both parents must be carriers
- Presents ages 5–35 (rare outside this range)
- Equal sex incidence; more severe hepatic disease in females
- No strong environmental triggers — purely genetic
- Prevalence ~1:30,000; carrier frequency ~1:90
02
Presentation
- Classic triad: liver disease + neuropsychiatric symptoms + Kayser-Fleischer rings
- Hepatic: ranges from asymptomatic elevation to acute liver failure or cirrhosis
- Neurologic: dysarthria, dysphagia, tremor (wing-beating), dystonia, parkinsonism
- Psychiatric: personality change, depression, psychosis (often misdiagnosed)
- Kayser-Fleischer rings: golden-brown copper deposits at corneal periphery (Descemet membrane)
- Coombs-negative hemolytic anemia — hallmark of acute copper release
03
Pathophysiology
- ATP7B mutation → dysfunctional hepatic copper-transporting ATPase
- Copper cannot be incorporated into ceruloplasmin or excreted into bile
- Free copper accumulates in hepatocytes → hepatocyte necrosis
- Overflow of free copper into blood → deposits in brain (basal ganglia), cornea, kidneys, RBCs
04
Diagnostics
- Slit-lamp exam: Kayser-Fleischer rings (present in >95% with neurologic disease, <50% hepatic-only)
- Serum ceruloplasmin: low (<20 mg/dL) in ~85% — useful screen but not diagnostic alone
- 24-hour urine copper: >100 µg/day (>40 µg/day in symptomatic patients) — key functional test
- Liver biopsy with quantitative copper: gold standard (>250 µg/g dry weight)
- Genetic testing: ATP7B mutation analysis confirms diagnosis; useful for family screening
05
Management
- First-line: D-penicillamine (copper chelator) — monitor for nephrotic syndrome, bone marrow suppression
- Alternative chelator: trientine — better tolerated, preferred if penicillamine intolerance
- Zinc acetate: blocks intestinal copper absorption; used for maintenance or presymptomatic patients
- Avoid copper-rich foods: shellfish, organ meats, nuts, chocolate, mushrooms
- Liver transplant: curative for acute liver failure or decompensated cirrhosis unresponsive to chelation
06
Clinical pivots
How to separate this script from the look-alikes that show up on exams and on the wards.
Autoimmune hepatitis
Wilson's lacks autoantibodies (ANA, anti-smooth muscle); check ceruloplasmin and urine copper in young patients with hepatitis.
Parkinson's disease
Wilson's affects patients <40 years old, has hepatic involvement, and shows Kayser-Fleischer rings absent in Parkinson's.
Hereditary hemochromatosis
Hemochromatosis accumulates iron (elevated ferritin, transferrin saturation) not copper; no Kayser-Fleischer rings.
Acute liver failure from other causes
Wilson's ALF is uniquely associated with Coombs-negative hemolytic anemia and a low/normal ALP despite severe hepatic necrosis.
Keep reading
Full libraryEducational use only. This illness script is a study framework, not medical advice. Confirm decisions with current guidelines and your clinical supervisors.