Case Presentation:

Recognition of clinically significant copper deficiency is increasing. Hematologically, it can present as anemia (microcytic, normocytic, or macrocytic) and neutropenia. Bone marrow findings can mimic myelodysplasia resulting in occasional inappropriate referral for bone marrow transplantation. It can manifest neurologically as myelopathy and peripheral neuropathy simulating subacute combined degeneration. Case Report: A 72-year-old female with known phlebotomy-dependent hemochromatosis, pernicious anemia, hypertension, hypothyroidism, and bipolar disorder presented with progressive generalized weakness, fatigue, and 26-lbs weight loss over several months. She reported symptoms of lower extremity numbness, tingling, and abnormal balance. Physical examination revealed pallor, decreased lower extremity deep tendon reflexes, and sensory ataxia. Complete blood count and smear showed macrocytic anemia, neutropenia, monocytosis, and enlarged platelets. Ferritin, TSH, zinc, erythropoietin, and RBC-folate were within normal. Cobalamin level was 869 pg/ml. Bone marrow biopsy showed myelodysplasia with no megaloblasts. Copper level was significantly low at <5 (normal 70-125 mcg/dL). Within four weeks of copper replacement, her macrocytic anemia resolved completely.


Copper is a trace element heavily involved in cell oxidation and signaling systems. Its metabolism is significantly interrelated to the metabolism of iron and zinc. The most common cause of copper deficiency is gastric surgery followed by excess zinc. Copper is required for the absorption and utilization of iron. Macrocytosis, neutropenia, and neurological manifestations are related to the role of copper as an important cofactor in enzymatic processes involved in cell division and protein synthesis. Copper supplementation tends to rapidly reverse the hematological abnormalities, but only stabilize the neurological manifestations. Copper levels should be checked in patients with suspected myelodysplasia or myeloneuropathy.


Hematological manifestations almost universally respond to copper supplementation, whereas neurological improvement is often reported as slow, incomplete, or even absent. The neurological sequelae of copper deficiency can be debilitating and irreversible, making prompt recognition and treatment essential for successful outcomes.