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

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-yearold 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. Copper deficiency is a rare cause of anemia and neutropenia that is characterized morphologically by cytoplasmic vacuolization in erythroid and myeloid precursors and ringed sideroblasts. There are a variety of causes of copper deficiency, including dietary deficiency, hypoproteinemic states (kwashiorkor, celiac disease, tropical and nontropical sprue, idiopathic hypoproteinemia, and enteropathy in infancy), excess excretion (nephrotic syndrome), Wilson disease, Menkes syndrome, and excess ingestion of zinc. 1 Given its low prevalence and nonspecific hematologic and clinical manifestations, the diagnosis of copper deficiency might be delayed. The bone marrow morphologic manifestations of copper deficiency are not widely appreciated. While not pathognomonic, the morphologic features are highly characteristic and might permit early diagnosis and correction of the deficiency state. We describe 3 patients with zinc-induced copper deficiency in whom the correct diagnosis first was suggested on the basis of bone marrow findings.