Copper deficiency: an unusual case of myelopathy with neuropathy

We read with interest the report of a case of myelopathy and neuropathy due to copper deficiency. ¹ Although this is the 55th reported case since the original description of myelopathy due to acquired copper deficiency in humans, ² it is likely that the condition remains under-recognized. In the North of England alone, five cases of copper deficiency myelopathy (CDM) have been diagnosed since the local index case raised awareness in late 2006. ³

The most common cause of CDM is previous upper gastrointestinal surgery, which was implicated in 47% of reported cases (review in preparation by authors). In the past, such surgery was typically performed for peptic ulcer disease, but with the advent of proton pump inhibitors and increasing levels of obesity, bariatric surgery is likely to take over as the leading risk factor. ⁴ The second most common cause of CDM is hyperzincaemia. In addition to the causes listed by the authors, denture cream can be a source of spurious zinc excess which has recently been associated with four cases of CDM and is easily missed by the unaware. ⁵ Although primary dietary copper deficiency could potentially give rise to CDM, such an association has not been reported to date.

Bertfield et al. (Ann Clin Biochem 2008;45:434–435) address the pathogenesis of the haematological manifestations, but not that of the neurological syndrome. It has been suggested that copper deficiency causes myelopathy through dysfunction of cytochrome oxidase, which is known to be copper-dependent. ⁶ However, this enzyme is not cobalamin-dependent, so this hypothesis does not readily explain the marked phenotypic parallels between CDM and subacute combined degeneration of the cord due to cobalamin deficiency (SCD). We have recently proposed that CDM and SCD share dysfunction of the methylation cycle as their final common pathway, which would explain their clinical and radiological similarity. ⁷

This is the first case in which copper supplementation was given intramuscularly. A parenteral route was chosen because the patient ‘would be unable to absorb oral supplements’. Although the absorptive surface for copper is reduced, oral supplementation has been effective in many similar cases so such an approach may not be necessary.

Finally, Bertfield et al. assert that ‘treatment with copper may prevent further neurological deterioration’. This is an understatement, since the neurological deficit of all reported cases did stabilize or improve on adequate copper replacement. Timely recognition and treatment are crucial in preventing potentially irreversible neurological disability.