Wilson's Disease
Summary
Wilson's Disease is a rare but treatable Autosomal Recessive disorder of copper metabolism caused by mutations in the ATP7B gene on Chromosome 13. The defect prevents the biliary excretion of copper, leading to toxic accumulation primarily in the Liver (causing cirrhosis/failure) and the Brain (specifically the Basal Ganglia, causing movement disorders). Diagnosis is often delayed due to the heterogeneous presentation, which can range from asymptomatic elevated LFTs to fulminant liver failure or acute psychosis. [1,2]
Key Facts
- Mechanism: ATP7B is a copper-transporting ATPase. Without it, copper cannot be loaded onto Ceruloplasmin or excreted into bile.
- Kayser-Fleischer (KF) Rings: Copper deposition in Descemet's Membrane of the cornea. Present in >95% of patients with neurological symptoms, but only 50% of those with hepatic symptoms.
- Ceruloplasmin: Low in 90% of patients. (Note: Ceruloplasmin is an acute phase reactant, so levels may be falsely "normal" in inflammation/hepatitis).
Clinical Pearls
The "Wing-Beating" Tremor: A classic sign where the held-out arms beat up and down like a bird's wings. It is a coarse, proximal tremor prominent on posture.
Alkaline Phosphatase (ALP) Paradox: In fulminant Wilson's liver failure, the ALP is paradoxically LOW (less than 40 IU/L) while Bilirubin is extremely high. This helps distinguish it from other causes of acute liver failure (viral/drug) where ALP is usually high.
Hemolysis: Acute release of free copper into the blood destroys red blood cells. A patient presenting with "Acute Hepatitis + Coombs Negative Hemolytic Anemia" has Wilson's until proven otherwise.
Demographics
- Prevalence: 1 in 30,000.
- Onset: Typically age 5 to 35. Can present up to age 50.
- Genetics: Autosomal Recessive. Carrier rate 1 in 90.
Copper Metabolism
- Dietary Intake: Absorbed in stomach/duodenum.
- Transport: Albumin carries copper to liver.
- Liver Processing:
- Incorporated into Ceruloplasmin by ATP7B.
- Excess excreted into Bile by ATP7B.
- Wilson's Defect: ATP7B fails.
- Low Ceruloplasmin (apoceruloplasmin degrades rapidly).
- Copper accumulates in hepatocytes -> necrosis -> leaks into blood -> deposits int Brain/Cornea/Kidney.
Hepatic (Children/Teens)
Neurological (Young Adults)
Psychiatric
- Eyes: KF Rings (Golden-brown ring at limbus). Best seen with Slit Lamp.
- Nails: Azure Lunulae (Blue moons).
- Abdomen: Stigmata of Chronic Liver Disease. Splenomegaly.
- Neuro: Assessment of tone, gait, and tremor.
Screening
- Serum Ceruloplasmin: Low (less than 0.2 g/L).
- Serum Copper: Low total copper (no ceruloplasmin), but High Free Copper (toxic).
- Urinary Copper: 24-hour collection. HIGH (>100 mcg/24h or >1.6 µmol).
- LFTs: AST > ALT typically. Low ALP.
Diagnostic
- Slit Lamp Exam: For KF rings.
- Liver Biopsy: Gold Standard. Quantifies hepatic copper (>250 mcg/g dry weight).
- Genetics: ATP7B mutation analysis (screening family members).
Imaging
- MRI Brain: "Face of the Giant Panda" sign in the midbrain (T2 hyperintensity). Atrophy of basal ganglia.
Management Algorithm
DIAGNOSIS CONFIRMED
↓
┌─────────────┼─────────────┐
ASYMPTOMATIC STABLE DISEASE ACUTE FAILURE
↓ ↓ (Wilsonian Crisis)
ZINC CHELATION THERAPY ↓
(Maintenance) (Penicillamine / LIVER TRANSPLANT
Trientine) (Life Saving)
1. Diet
- Avoid high copper foods: Shellfish, Liver, Chocolate, Nuts, Mushrooms.
2. Medical Therapy (Lifelong)
- Chelating Agents (Remove copper via urine):
- Penicillamine: Traditional first line.
- Mechanism: Binds copper.
- Side Effects: Nephrotic syndrome, SLE-like syndrome, Bone marrow suppression, deterioration of neuro symptoms initially.
- Co-prescribe: Pyridoxine (Vitamin B6) as it is an antagonist.
- Trientine: Second line (or first line if neuro symptoms). Fewer side effects.
- Penicillamine: Traditional first line.
- Zinc Acetate:
- Mechanism: Induces Metallothionein in gut cells, which binds copper and prevents absorption.
- Use: Maintenance therapy or presymptomatic patients.
3. Surgical
- Liver Transplant: Curative. Indicated for Fulminant Failure or Decompensated Cirrhosis unresponsive to medical therapy. The new liver has functional ATP7B.
- Neuro Worsening: 20% of patients get worse when starting Penicillamine (mobilised copper enters brain).
- Renal: Fanconi Syndrome (Tubular damage).
- Osteoporosis/Rickets.
- Excellent: If treated before permanent damage. Normal life expectancy.
- Liver Failure: Fatal without transplant.
- Neuro: Symptoms often improve with chelation but may be permanent if scarring occurred.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Wilson's Disease | EASL (2012) / AASLD | Screen all first-degree relatives. Penicillamine is effective but monitor renal function. |
| Monitoring | EASL | Monitor 24h urinary copper to ensure chelation is working. |
Landmark Knowledge
1. The Penicillamine Paradox
- Neurological patients are often started on Trientine instead of Penicillamine because Penicillamine causes a rapid mobilisation of copper stores which can acutely flood the brain, causing irreversible neurological decline.
What is Wilson's Disease?
It is a genetic condition where your body cannot get rid of excess copper from food. Copper is a trace metal we need in small amounts, but too much is poisonous.
Where does the copper go?
It builds up in the liver first. When the liver is full, it overflows into the blood and settles in the brain and eyes.
How do we treat it?
We use "chelating agents" - medicines that act like a magnet for copper, grabbing it from the blood and flushing it out in your urine. You will need to take these (or Zinc) for the rest of your life.
Can I eat chocolate?
You should avoid it, along with shellfish and nuts, especially at the start of treatment. Once your copper levels are under control, you can have small amounts.
Primary Sources
- European Association for Study of Liver (EASL). EASL Clinical Practice Guidelines: Wilson's disease. J Hepatol. 2012;56:671-685.
- Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson disease: an update. AASLD Practice Guidelines. Hepatology. 2008.
Common Exam Questions
- Genetics: "Inheritance pattern?"
- Answer: Autosomal Recessive.
- Biochemistry: "Ceruloplasmin level?"
- Answer: Low (less than 0.2).
- Clinical Signs: "Kayser-Fleischer rings location?"
- Answer: Descemet's membrane of the Cornea.
- Medicine: "Acute Hepatitis + Low ALP?"
- Answer: Wilson's Disease.
Viva Points
- Face of the Giant Panda: MRI sign in midbrain. Red nucleus/Substantia nigra (dark) vs Tegmentum (bright).
- Treatment in Pregnancy: Do NOT stop treatment. Fulminant liver failure can occur. Reduce dose of Penicillamine in 3rd trimester (wound healing risk).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.