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Zinc-Induced Copper Deficiency
A Report of Three Cases Initially Recognized on Bone Marrow Examination

Monte S. Willis MD, PhD, Sara A. Monaghan MD, Michael L. Miller DO, Robert W. McKenna MD, Wiley D. Perkins MD, Barry S. Levinson MD, Vikas Bhushan MD, Steven H. Kroft MD
DOI: http://dx.doi.org/10.1309/V6GVYW2QTYD5C5PJ 125-131 First published online: 1 January 2005


Copper deficiency is a rare cause of sideroblastic anemia and neutropenia that often is not suspected clinically. The morphologic findings in bone marrow, while not pathognomonic, are sufficiently characteristic to suggest the diagnosis, leading to further testing to establish the correct diagnosis. Excess zinc ingestion is among the causes of copper deficiency. We present 3 cases of zinc-induced copper deficiency in which the diagnosis first was suggested on the basis of bone marrow examination. The first patient was a 47-year-old man with a debilitating peripheral neuropathy that had progressed during the previous 18 months, mild anemia, and severe neutropenia. The second was a 21-year-old man receiving zinc supplementation for acrodermatitis enteropathica in whom moderate normocytic anemia and neutropenia developed. The third patient was a 42-year-old man with anemia, severe neutropenia, and a peripheral neuropathy that had progressed during 8 months. The bone marrow findings in all cases suggested copper deficiency, which was confirmed by further laboratory testing and determined to be due to zinc excess. The morphologic features, clinical manifestations, differential diagnosis, and pathogenetic mechanisms are discussed.

Key Words:
  • Zinc toxicity
  • Copper deficiency
  • Cytoplasmic vacuoles
  • Sideroblastic anemia
  • Ringed sideroblasts