Hypocupremia and bone marrow failure

Abstract

Hypocupremia and bone marrow failureCopper deficiency associated with neurological disorders is a well-documented condition. However, hypocupremia is less often recognized as a cause of cytopenias or bone marrow failure. We report an illustrative series of three new cases of bi-lineage cytopenia associated with copper deficiency. We have analyzed clinical features of current and historical cases to identify clues that could facilitate application of appropriate laboratory testing and heighten the level of clinical suspicion. By maintaining an appropriately high level of suspicion for potential copper deficiency and obtaining a serum copper level, bone marrow failure due to this condition can be correctly diagnosed and treated. We suggest that copper deficiency be included in the differential diagnosis of reversible causes of bone marrow failure syndromes including myelodysplastic syndrome. 93:e1-e5 DOI: 10.3324/haematol.12121 IntroductionIn the evaluation of patients with pancytopenia, reversible causes of bone marrow failure such as nutritional deficiencies, viral infections, and medications need to be considered in the differential diagnosis. Copper deficiency can be easily treated but the diagnosis may be difficult due to comorbidities and low level of clinical suspicion.Patients with copper deficiency most commonly present with neurological disorders, including myeloneuropathy, arthralgias and neuropathy. [1][2][3][4] A diagnosis of copper deficiency is usually established by measuring serum copper or ceruloplasmin levels; a serum copper level <10 ∝mol/L or ceruloplasmin <180 mg/L is considered presumptive evidence of copper deficiency. The most common hematologic abnormalities associated with copper deficiency include anemia and neutropenia, while the platelet count usually remains normal.The adult diet in Western countries contains 0.6 to 1.6 mg of copper/d. Water, shellfish, organ meats, nuts, and grains are all sources of dietary copper. Absorption occurs through the intestinal mucosa across the basement membrane into the blood stream via energy dependent mechanisms where the availability and saturation of copper may limit absorption. Of significant interest is the physiologic relationship between copper and zinc. High zinc levels result in increased metallothionin production in enterocytes. The high affinity of copper to metallothionin displaces zinc and thus leads to the accumulation of copper in the enterocytes. The enterocytes are ultimately shed into the gastrointestinal tract, leading to copper elimination. 5 Copper plays a role as a cofactor for many enzymes, in electron-transporting proteins, and in antioxidant metabolism. The main copper-binding protein is ceruloplasmin which plays a role in copper transport and release and in protection of cells from oxidative damage. Both ferroxidase and ceruloplasmin may oxidize Fe 2+ to Fe 3+ facilitating the release of Fe from ferritin and its binding to transferrin. 6 Copper is required for a variety of enzymes, including amino oxidase, ferroxidase, c...

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