Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published October 4, 2017


An increased signal in the posterior columns of the spinal cord on T2-weighted MRI images can be due to a number of diseases. Metabolic causes are the most common, among which subacute combined degeneration due to vitamin B12 deficiency is the classic cause. Other metabolic causes include folate deficiency, vitamin E deficiency, and copper deficiency. Read the latest Clinical Problem-Solving article.

Clinical Pearls

Q: Who is at risk for copper deficiency?

A: Certain patient populations are susceptible to copper deficiency. Patients who have undergone bowel surgery or bypass surgery and patients with celiac disease are at risk, as are persons who receive intravenous nutrition without copper replacement. Copper deficiency is well recognized in persons who use zinc-based denture creams in excess; it is also reported in persons taking zinc supplements. Rarely, hypocupremia occurs as a result of a hereditary condition, such as Menkes disease, an x-linked disorder that is caused by a mutation in the protein that mediates the uptake of copper in the enterocytes. Up to 20% of cases of copper deficiency may be idiopathic.

Q: What is the mechanism by which zinc excess leads to copper deficiency?

A: Copper absorption occurs in the stomach and proximal duodenum. When zinc is ingested, it upregulates metallothionein in the enterocytes. Metallothionein is an intracellular ligand that binds copper with a much higher affinity than zinc. An increased intake of zinc leads to an increased upregulation of metallothionein, and therefore more metallothionein preferentially binds copper. This bound copper remains in the enterocytes and is lost in the feces when intestinal cells are sloughed, which leads to hypocupremia.

Morning Report Questions

Q: What are some of the manifestations of copper deficiency?

A: Serum levels of ceruloplasmin and copper are low in all patients with copper deficiency. Urinary copper excretion is typically low but may be normal. Patients with myelopathy caused by copper deficiency typically present with gait difficulty, paresthesias of the hands or feet, and cytopenias. They have sensory ataxia due to dorsal column dysfunction, sensory or motor neuropathy (or both) manifesting as diminished distal reflexes, sensory loss in a stocking-and-glove distribution (limited to the feet and hands), and sometimes spastic paraparesis. Upper motor neuron signs, are often, but not invariably, present. Hematologic abnormalities, including leukopenia or anemia, typically precede neurologic manifestations of copper deficiency. The anemia is typically macrocytic, although normocytic and microcytic anemias have been described. In addition to the neurologic and hematologic manifestations addressed above, skeletal abnormalities including osteoporosis and other bony lesions may occur in adults and children with copper deficiency. Bone marrow biopsy may reveal vacuolated myeloid and erythroid precursors, ringed sideroblasts, and multilineage dysplasia — findings that are consistent with the myelodysplastic syndrome.


Figure 1. Magnetic Resonance Imaging of the Spine in a Patient with Copper Deficiency.

Q: Are the hematologic and neurologic symptoms of copper deficiency fully reversible with treatment?

A: Hematologic abnormalities generally resolve with copper supplementation, but neurologic responses are more variable. In one review of 16 patients with copper deficiency, cytopenia resolved in 14 of 15 patients (93%) within 8 to 12 weeks after the initiation of copper supplementation, whereas among the 12 patients with neurologic symptoms and signs, 3 (25%) had a partial reduction of sensory and motor symptoms, 5 (42%) had no further deterioration, and 4 (33%) had progressive disease despite treatment. In another review of 55 patients, of whom 47 had reported neurologic outcomes, 24 patients (51%) had stabilization of symptoms and 23 patients (49%) had partial reduction of symptoms after the initiation of copper supplementation.

Browse more Clinical Pearls & Morning Reports »