Wilson’s Disease
Background Information
Definition
Wilson’s disease is an autosomal recessive disorder of copper metabolism, resulting in progressive accumulation of copper in multiple organs.
Aetiology
Autosomal recessive mutation in the ATP7B gene on chromosome 13
- ATP7B gene encodes for a copper-transporting ATPase in the liver
- ↓ Incorporation of copper into apoceruloplasmin → ↓ serum ceruloplasmin → ↓ free serum copper → copper accumulates in organs
Clinical Manifestation
Suspect Wilson’s disease in a young patient (5-40 y/o) with:
- Chronic liver disease, and
- Psychiatric symptoms or neurological symptoms (esp. movement disorder), and
- +ve Family history
Most common manifestations (based on affected organs):
| Liver |
|
| Brain (→ neurological features) | Neurological features:
Movement disorders:
|
| Brain (→ psychiatric features) |
|
| Eyes |
|
Other less common manifestations:
| Blood |
|
| Renal |
|
| MSK |
|
Diagnosis
Work-up of suspected Wilson’s disease:
- Slit lamp examination (for Kayser-Fleischer rings)
- Copper studies
- 1st line: serum caeruloplasmin
- 2nd line: 24-hour urinary copper
Copper Studies
| Test | Findings in Wilson’s disease |
|---|---|
| Serum caeruloplasmin | Low |
| 24-hour urinary copper | High |
| Total serum copper | Low |
| Free serum copper (non-ceruloplasmin-bound copper) | High |
Serum caeruloplasmin is the copper study test of choice in the context of Wilson’s disease.
Total serum copper and free (non-caeruloplasmin-bound) copper are not recommended for the diagnosis of Wilson’s disease and are mainly used for monitoring response to treatment.
Blood Tests
Wilson’s disease primarily gives a hepatocellular pattern on LFTs:
- ↑ AST and ALT (mild typically <300 IU/L)
- Normal GGT ALP
- ↑ Bilirubin
FBC:
- Coombs -ve haemolytic anaemia (i.e. non-immune haemolytic anaemia) (due to direct toxicity to RBCs)
- Thrombocytopaenia and leukopaenia (due to hypersplenism from portal hypertension)
Further Studies
Imaging:
- Abdominal ultrasound – all patients
- MRI brain – all patients
- Consider transient elastography (e.g. FibroScan)
The following are NOT routinely required for diagnosis:
- Genetic testing
- Liver biopsy
Management
Definitive Management
Offer lifelong copper chelation therapy
- 1st line: penicillamine
- 2nd line: trientine
- 3rd line: zinc salts (only in selected cases, to be started by a specialist)
24-hour urinary copper is the key test used to monitor treatment response.
Copper chelation therapy is safe for both pregnancy and breastfeeding.
The only curative treatment is liver transplantation
- Indicated in children with decompensated liver disease + encephalopathy
- Consider in adults with acute liver failure
General / Conservative Management
Lifestyle Advice
Avoid foods high in copper:
- Shellfish
- Liver and other offal
- Chocolate
- Nuts
- Mushrooms
Genetic Screening
Clinical + biochemical + genetic screening should be offered to all 1st degree relatives.
Complication Screening
If the patient develops cirrhosis, screen for the following complications (also see the Cirrhosis article for more information):
| Complication | Test |
|---|---|
| Hepatocellular carcinoma | Ultrasound +/- every 6 months |
| Oesophageal varices | Perform upper GI endoscopy after diagnosis (unless planning to take carvedilol or propranolol) |