Low ceruloplasmin concentrations are seen in a majority of cases of Wilson’s disease, which is an autosomal recessive condition. The gene for Wilson’s disease has been cloned. The gene product is probably a copper transporting ATPase (ATP7B) which affects copper transport at a common point resulting in both defective biliary excretion and incorporation into ceruloplasmin. Already at least 27 different mutations in the gene have been identified which is located on chromosome 13. Mutations in a related gene encoding or a second ATPase (ATP7A), located on the X chromosome, are responsible for the copper transport defects which are manifest in Menkes disease. The gene encoding for ceruloplasmin is found on chromosome 3. Whilst mutations in this gene have been described, they are not associated with the clinical manifestations of Wilson’s disease. The clinical features, which may become manifest between ages six and 50 years but most commonly appear between late childhood and early adult life, are a result of the fact that copper in the free form exhibits considerable toxicity for certain tissues when it accumulates to excess concentrations, whereas ceruloplasmin-copper complexes are nontoxic.
The diagnosis of Wilson’s disease rests on five cardinal points: first, the unequivocal demonstration of Kayser-Fleischer rings; second, the presence of a serum ceruloplasmin below the normal range; third, if liver biopsy is possible in the face of clotting abnormalities, the demonstration of copper content in excess of 250 mg per gram of dry liver; fourth, and less reliable, the urinary excretion of copper of more than 1 m mole/24 hours. The final arbiter is to assess the incorporation of 64Cu into ceruloplasmin. In patients presenting with neurological symptoms, the documentation of Kayser-Fleischer rings and the measurement of serum ceruloplasmin are usually sufficient for the diagnosis. In patients presenting with liver disease, the presence of Kayser-Fleischer rings and a low ceruloplasmin may be present in only 65% with subsequently proven Wilson’s disease. It is here that measurement of hepatic copper content and, if necessary, assessment of 64Cu incorporation may be necessary. In all patients presenting with clinical or histological evidence of chronic hepatitis, the diagnosis of Wilson’s disease must be entertained once viral and autoimmune causes have been eliminated.
Sample requirement: 2 mL serum.
Age Serum Ceruloplasmin (g/L)
|< 4 months||0.09 – 0.27|
|4 months-1 year||0.14 – 0.41|
|1-10 years||0.24 – 0.47|
|10-13 years||0.18 – 0.27|
|> 13 years (adult)||0.24 – 0.71|
Centres offering this assay:
Sheffield Northern General’s PRU Diagnostic Service