Scottish Trace Element and Micronutrient Reference Laboratory
Scotland's specialised laboratory for trace elements and vitamins in health and disease
Disorders of Copper Metabolism
There are several familial disorders of copper metabolism. The best known is hepatolenticular degeneration (Wilson's Disease). This is related to an inability to excrete Cu normally in bile, leading to toxic accumulation in the liver, brain and kidney.
The condition presents in childhood or early adolescence as unexplained hepatic and/or neurological disease. The usual biochemical finding is of low plasma Cu and caeruloplasmin concentrations. There is however, a marked increase in urine copper excretion, outputs up to 5-10 times normal being observed. Treatment with penicillamine further increases urine copper output and a sustained copper diuresis leads to remission of symptoms, provided diagnosis is made early and treatment instituted before irreversible neurological damage has occurred. Family screening is required to detect asymptomatic homozygous siblings who must receive penicillamine for life. A rare form of presentation is as fulminant liver disease, with no previous history of illness. In these usually fatal cases there is massive release of Cu stored in the liver resulting in a sudden haemolytic crisis and hepato-renal failure. Plasma Cu is very high and there is an increase in the plasma Cu fraction not bound to caeruloplasmin.
In both types of presentation there may be difficulties of diagnosis caused by active liver disease. The determination of the Cu content of a needle biopsy of liver and histological examination may be required.
All unexplained cases of neurological or liver disease in adolescents should be investigated to exclude Wilson's Disease, which is one of the few treatable inborn errors.
Menkes Syndrome or 'steely hair' disease is an even rarer, usually fatal, disorder of Cu metabolism. This presents in young children as growth failure, and severe neurological disease with arterial and bone lesions. It is thought to involve a failure of Cu transport across cell membranes, including those in the intestinal mucosa. The effect is to produce severe intracellular Cu deficiency.
A condition of Cu accumulation known as 'Indian Childhood Cirrhosis' has been described. Certain other rare forms of neurological disease are Cu related.
Return to Copper