Serum
g/L
Wilson disease is an autosomal recessive disorder that occurs in ~1 in 30,000 individuals in Europe and North America. It is caused by a mutation of a gene on chromosome 13, coding for a membrane bound copper transporting ATPase known as ATP7B. More than 100 mutations of this gene have been discovered, explaining the variable clinical presentation of Wilson disease. This mutation results in 2 defects in hepatic copper metabolism: a decrease in the incorporation of copper into caeruloplasmin and diminished biliary excretion of copper. Hepatic copper concentration gradually increases and injures hepatocytes. Excess copper escapes into the circulation and is deposited in basal ganglia, cerebral cortex, kidney, and cornea. Free copper is toxic and damages these tissues.
Normally, caeruloplasmin is synthesized in hepatocytes as an apo-caeruloplasmin and secreted into the plasma after copper is incorporated into a metal-binding motif, forming holo-caeruloplasmin. Failure of copper incorporation into caeruloplasmin results in loss of its enzymatic activity and rapid degradation by plasma proteases. In patients with Wilson disease, loss of ATP7b activity results in failure of copper incorporation into caeruloplasmin, secretion of apo-caeruloplasmin, and rapid degradation. Low plasma caeruolplasmin concentration is the hallmark of Wilson disease.
Individuals with Wilson disease are not usually diagnosed until after their 4th or 5th year. Some patients are not diagnosed until their early 20s. They usually present with liver disease, neurologic or psychiatric symptoms.
The most common laboratory finding is a low plasma caeruloplasmin. Other laboratory findings include:
Low caeruloplasmin is detected in 95% of homozygotes and 20% of heterozygotes. Low levels need to be interpreted cautiously because any type of severe liver disease may interfere with caeruloplasmin synthesis. Low concentrations also occur with malnutrition and protein loss. Falsely normal caeruloplasmin values can be seen with oestrogen therapy, pregnancy, and acute inflammation.
First degree relatives of patients newly diagnosed with Wilson disease must be screened. Assessment includes history, physical examination, slit lamp examination of eyes, liver function tests, serum copper, caeruloplasmin, and 24 hour urinary copper. Individuals without Kayser Fleischer rings who have subnormal caeruloplasmin and abnormal liver function tests should undergo further testing for ATP7B gene mutations. In populations of Northern European descent, the H1069Q mutations accounts for at least 40% of disease alleles, whereas in Far East Asian populations an R778L mutation occurs in 30% of affected individuals.
Local test
7 days
Can be added on to an existing request up to 4 days following sample receipt
30 days
Specimen Labelling Procedure
8210
