Copper Deficiency: A Forgotten Disorder?

Copper is an essential trace element that is required for the function of a number of enzymes necessary for normal metabolic activities including ferroxidase I (ceruloplasmin) which functions to release iron from cells with mobilizable iron stores. Copper deficiency is well reported in the literature but is considered relatively rare. It appears primarily to result from poor absorption, even though the precise mechanism(s) may not be apparent in all cases. Importantly, copper deficiency is a masquerader. It frequently results in manifestations that could easily be mistaken for another condition leading potentially to misdiagnosis and inappropriate therapy. Unlike vitamin B12 and folate deficiencies however, many guidelines and textbooks make no mention of copper deficiency as a potential secondary cause for a myelodysplasia (MDS)-like presentation or neuropathy even though multiple reports have described these associations.

In order to formally explore physician awareness about copper deficiency at our own institution we reviewed the medical records of 46 patients that were referred to the department of Hematology and/or Neurology at the Louisville Veterans Affairs Medical Center by their primary care physicians during the year 2010. 23 (49%) and 24 (51%) patients were referred for cytopenia (s) / macrocytosis and/or peripheral neuropathy respectively. however; no clearly identifiable etiology was found. Among patients with cytopenia (s) / macrocytosis, 34.8% (n=8) had concomitant peripheral neuropathy, 91.3% (n=21) presented with anemia as a part of their cytopenia (s); of those, 43% (n=9) were deficient in Iron without any clear etiology and 8.7% (n=2) were diagnosed with myelodysplatic syndrome. 100% (23) of patients with cytopenia (s)/macrocytosis were evaluated for Folic Acid and B12 deficiency either by their Primary care physician or hematologist. Only two patients (8.7%) were diagnosed with B12 deficiency, of those, one (4.3%) was referred because of isolated macrocytosis with a normal serum copper level checked by the hematologist. 100% (n=24) of patients referred to the neurology clinic with peripheral neuropathy were evaluated for Folic Acid and B12 deficiency, all with normal results. However, none were evaluated for copper deficiency including one patient with a history of gastric bypass surgery. Among these patients, 47.8% (n=11) were identified with isolated peripheral neuropathy, 8.3% with concomitant anemia, 8.3% with thrombocytopenia, 33.3% (n=8) with diabetes mellitus or impaired glucose tolerance test, 12.5% (n=3) with a history of alcohol abuse, 4.2% (n=1) with a positive HIV test and 4.2% (n=1) with a history of gastric bypass surgery with concomitant thrombocytopenia.

Our study albeit small and from a single institution points to a significant lack of awareness among physicians about copper deficiency as a possible diagnostic consideration in patients with cytopenias and/or neuropathy even though it has been clearly reported in the literature to be associated with a clinical presentation very similar to B12 deficiency. We believe that this is representative of the prevailing practice pattern in the medical community as a whole. It is understandable therefore that we do not really know the true incidence of a disorder that is rarely tested even in patients presenting with known clinical features associated with it. Finally, one of the most compelling reasons to recognize copper deficiency is that like B12 deficiency, this is a potentially devastating condition that is treatable with simple replacement therapy.

The contents of this abstract do not represent the views of the Department of Veterans Affairs or the US government.

No relevant conflicts of interest to declare.