Makindo Medical Notes

Related Subjects: |Chronic liver disease |Cirrhosis |Alkaline phosphatase (ALP) |Liver Function Tests |Ascites Assessment and Management |Budd-Chiari syndrome |Autoimmune Hepatitis |Primary Biliary Cirrhosis |Primary Sclerosing Cholangitis |Wilson disease |Hereditary Haemochromatosis |Alpha-1 Antitrypsin (AAT) deficiency |Non alcoholic steatohepatitis (NASH) |Spontaneous Bacterial Peritonitis |Alcoholism and Alcoholic Liver Disease

Wilson's disease accounts for 6-12% of all patients with acute liver failure referred for emergency transplantation. Wilson's disease should be considered in any individual with liver abnormalities or neurological movement disorders of uncertain cause. Age alone should not be used to eliminate a diagnosis of Wilson's disease.

About

• Wilson's disease is an autosomal recessive disorder of copper transport.
• It occurs in approximately 1 in 30,000 live births.
• Without treatment, it leads to cirrhosis, neurological problems, and ultimately, death.
• Early diagnosis is critical for initiating treatment to prevent irreversible damage.

Aetiology

• Wilson's disease is caused by a mutation in the ATP7B gene on chromosome 13, which is seen in 1 in 90 people.
• Over 200 mutations in the ATP7B gene have been reported, resulting in impaired copper transport.
• The copper-transporting ATPase encoded by this gene is responsible for excreting copper into the biliary system for elimination.

Kayser-Fleischer rings are caused by the deposition of copper in Descemet's membrane of the cornea. They are not entirely specific for Wilson's disease but are a key diagnostic feature.

Clinical Features

• Symptoms can begin between the ages of 5 and 45.
• Neurological and psychiatric symptoms are more common in younger patients.
• Kayser-Fleischer rings are best seen with slit lamp examination, appearing at the corneal-scleral margin. They resolve with treatment.
• Anaemia and jaundice due to haemolysis and cirrhosis—free copper causes oxidative damage to red blood cell membranes.
• Sunflower cataracts may appear on the posterior surface of the lens.
• Acute or chronic hepatitis, progressing to cirrhosis, hepatosplenomegaly, and jaundice.
• Neurological features include dysarthria, dystonia, rigidity, tremor, and choreoathetosis (due to copper deposition in the basal ganglia).
• Psychiatric symptoms such as irritability, anger, and poor self-control.
• Osteoporosis and rickets can occur due to chronic disease.

Investigations

• Elevated liver transaminases (ALT, AST).
• Prolonged prothrombin time (PT) in advanced liver disease.
• Coombs-negative haemolytic anaemia.
• Low serum caeruloplasmin (<0.2 g/L).
• Elevated free serum copper (>1.6 micromol/L).
• High urinary copper excretion (>1.6 micromols/24 hrs).
• Increased hepatic copper content (>250 mcg/kg of dry weight).
• Renal tubular defect—evident in urine through proteinuria, glycosuria.
• MRI may show basal ganglia and cerebellar changes, with the "giant panda" sign.
• Genetic testing for the ATP7B mutation can confirm the diagnosis but is complicated by the high number of mutations.

The combination of Kayser-Fleischer rings and low serum ceruloplasmin (<0.1 g/L) is sufficient to establish a diagnosis of Wilson's disease.

Management

• Untreated Wilson's disease is universally fatal, with most patients dying from liver or neurological complications. Chelation therapy and liver transplantation have significantly improved survival.
• Copper chelation therapy with D-penicillamine is the first-line treatment, but it can cause side effects such as lupus-like syndrome and nephrotic syndrome. Pyridoxine supplementation is recommended to avoid deficiency.
• Dietary copper restriction is necessary to reduce copper intake.
• Zinc acetate can block gastrointestinal copper uptake and is a safe, non-toxic alternative to D-penicillamine.
• Triethylene tetramine dihydrochloride is another option for copper chelation.
• Liver transplantation is curative for patients with advanced liver disease.

References

• EASL Clinical Practice Guidelines: Wilson's disease 2012