Update on anemia and neutropenia in copper deficiency

Copper deficiency is an under-recognized cause of reversible refractory anemia and leukopenia, particularly neutropenia, often misdiagnosed as myelodysplastic syndrome (MDS). Clinicians and hematopathologists need to be aware of distinct morphologic findings to distinguish these entities including cytoplasmic vacuolization of both erythroid and myeloid precursors, excess iron stores, ringed sideroblasts, iron incorporation in plasma cells, and variable marrow cellularity. In contrast, the findings in MDS do not include myeloid lineage vacuolization, abnormal nuclear lobulation of both erythroid and myeloid precursors, nuclear/cytoplasmic dyssynchrony, or dysmegakaryopoiesis with abnormalities of nuclear lobulation and size.

The mechanism of neutropenia remains unknown; however, the study by Peled and coworkers suggests that copper deficiency results in the inhibition of differentiation and self-renewal of CD34(+) hematopoietic progenitor cells. A number of recent studies have reported on the association of copper deficiency with the development of concomitant neurologic deficits manifested as peripheral neuropathies and myeloneuropathy indistinguishable from the findings seen in vitamin B12 deficiency.

Patients presenting with refractory anemia and leukopenia with or without associated neurologic deficits should have copper and ceruloplasmin levels measured as part of their diagnostic evaluation.