A 46-year-old woman comes to the office due to worsening lower extremity tingling and numbness. She has also had difficulty walking, especially at night. Review of systems is positive for hair loss. The patient had gastric bypass surgery 5 years ago and has lost 30 kg (66 lb). She was originally prescribed multivitamin and mineral supplements but now takes only zinc. Physical examination shows gait ataxia with loss of vibration and position sensation in the feet. Romberg sign is present. There is mild lower extremity edema, scattered skin depigmentation, and fragile hair. Laboratory studies reveal microcytic anemia and leukopenia. Deficiency of which of the following is the most likely cause of this patient's current condition?
Clinical manifestations of trace mineral deficiencies | |
Chromium |
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Copper |
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Iron |
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Selenium |
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Zinc |
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This woman with distal extremity paresthesia, loss of vibration sense and proprioception (eg, Romberg sign), and ataxia has peripheral neuropathy. In association with anemia, skin depigmentation, fragile hair, and edema, this presentation suggests copper deficiency. Acquired copper deficiency is most often due to malabsorption from prior gastric surgery (eg, bariatric surgery). Other risk factors include chronic malabsorptive syndromes (eg, inflammatory bowel disease, celiac disease) and excessive ingestion of zinc, which competes with copper for absorption in the gastrointestinal tract.
Copper is a required cofactor in many enzymes, including those involved with protein synthesis, cellular division, iron absorption, and normal central nervous system function. Neurologic manifestations are often the presenting symptoms and begin several years after surgery with a slowly progressive myeloneuropathy similar to subacute combined degeneration from B12 deficiency (eg, paresthesia, numbness, sensory ataxia). Myelopathic symptoms (eg, spasticity, upper motor neuron signs) occur in advanced disease.
Hematologic abnormalities are also characteristic. Microcytic anemia occurs from copper deficiency–induced impairment of iron absorption, although macrocytic or normocytic anemia is also common. Leukopenia may also occur. Other symptoms include hair fragility, skin depigmentation, hepatosplenomegaly, edema, and osteoporosis. The diagnosis is confirmed with low serum copper and ceruloplasmin levels; management includes copper supplementation and discontinuation of zinc.
(Choice B) Selenium deficiency causes cardiomyopathy and macrocytosis, as well as immune and thyroid dysfunction. It does not typically cause neuropathy or microcytic anemia.
(Choice C) Folate deficiency typically causes a megaloblastic, macrocytic anemia (mean corpuscular volume >100 μm3); neurologic dysfunction and skin changes would be unexpected.
(Choice D) Vitamin C deficiency classically causes scurvy, which is characterized by petechiae, perifollicular hemorrhage, gingivitis, bruising, and poor wound healing, none of which is seen in this patient.
Educational objective:
Copper deficiency typically occurs in patients with a history of gastric surgery (eg, bariatric), chronic malabsorption (eg, inflammatory bowel disease), or excessive zinc ingestion. Symptoms include slowly progressive myeloneuropathy similar to that of vitamin B12 deficiency (eg, distal extremity paresthesia, numbness, sensory ataxia), anemia, hair fragility, skin depigmentation, hepatosplenomegaly, edema, and osteoporosis.