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July 12, 2004

Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration


Background: Copper deficiency in ruminants is known to cause an ataxic myelopathy. Copper deficiency as a cause of progressive myelopathy in adults is underrecognized.
Objective: To describe the clinical, biochemical, electrophysiologic, and imaging characteristics in 13 patients with myelopathy associated with copper deficiency.
Methods: The records of patients with a copper deficiency–associated myelopathy were reviewed. Clinical characteristics, laboratory investigations, and responses to therapeutic intervention were summarized.
Results: Thirteen such patients were found, 11 of them in a 15-month period. All patients presented with prominent gait difficulty, reflecting a sensory ataxia due to dorsal column dysfunction and lower limb spasticity. All patients had polyneuropathy. A high or high-normal serum zinc level was seen in 7 of the 11 patients for whom this information was available. Somatosensory evoked potential studies done in eight patients showed impaired conduction in central proprioceptive pathways. Dorsal column signal change on spine MRI was present in three patients. An initial clue to the diagnosis was a very low ceruloplasmin level; further tests of copper metabolism excluded Wilson disease. The cause remained unexplained in most patients. Oral copper supplementation restored normal or near-normal copper levels in 7 of the 12 patients in whom adequate follow-up data were available; parenteral supplementation restored normal level in 3 further patients. Copper supplementation prevented further neurologic deterioration, but the degree of actual improvement was variable.
Conclusions: Unrecognized copper deficiency appears to be a common cause of idiopathic myelopathy in adults. The clinical picture bears striking similarities to the syndrome of subacute combined degeneration associated with vitamin B12 deficiency. Early recognition and copper supplementation may prevent neurologic deterioration.

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Kumar N, Gross JB Jr, Ahlskog JE. Myelopathy due to copper deficiency. Neurology. 2003; 61: 273–274.
Schleper B, Stuerenburg HJ. Copper deficiency-associated myelopathy in a 46-year-old woman. J Neurol. 2001; 248: 705–706.
Prodan CI, Holland NR, Wisdom PJ, Burstein SA, Bottomley SS. CNS demyelination associated with copper deficiency and hyperzincemia. Neurology. 2002; 59: 1453–1456.
Gregg XT, Reddy V, Prchal JT. Copper deficiency masquerading as myelodysplastic syndrome. Blood. 2002; 100: 1493–1495.
Kumar N, McEvoy KM, Ahlskog JE. Myelopathy due to copper deficiency following gastrointestinal surgery. Arch Neurol. 2003; 60: 1782–1785.
Jubb KVF, Huxtable CR. The nervous system. In: Jubb KVF, Kennedy PC, Palmer N, eds. Pathology of domestic animals. 4th ed. San Diego: Academic Press, 1993: 267–439.
Bennetts HW, Chapman FE. Copper deficiency in sheep in Western Australia: a preliminary account of the aetiology of enzootic ataxia of lambs and anaemia of ewes. Aust Vet J. 1937; 13: 138–149.
Menkes JH, Alter M, Steigleder GK, Weakley DR, Sung JH. A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics. 1962; 29: 764–779.
Kaler SG, Gallo LK, Proud VK, et al. Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus. Nat Genet. 1994; 8: 195–202.
Danks DM, Campbell PE, Stevens BJ, Mayne V, Cartwright E. Menkes’ kinky hair syndrome. An inherited defect in copper absorption with widespread effects. Pediatrics. 1972; 50: 188–201.
Danks DM, Cartwright E, Stevens BJ, Townley RR. Menkes’ kinky hair disease: further definition of the defect in copper transport. Science. 1973; 179: 1140–1142.
Tan N, Urich H. Menkes’ disease and swayback—a comparative study of two copper deficiency syndromes. J Neurol Sci. 1983; 62: 95–113.
Alleyne T, Adogwa A, Lalla A, Joseph J, John R. Novel mitochondrial proteins and decreased intrinsic activity of cytochrome-c oxidase. Characteristics of swayback disease in sheep. Mol Chem Neuropathol. 1996; 28: 285–293.
Pedespan JM, Jouaville LS, Cances C, et al. Menkes disease: study of the mitochondrial respiratory chain in three cases. Eur J Paediatr Neurol. 1999; 3: 167–170.
Bottomley SS. Sideroblastic anemias. In: Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM, eds. Wintrobe’s clinical hematology. 10th ed. Baltimore: Williams & Wilkins, 1999: 1022–1045.
Prodan CI, Holland NR. CNS demyelination from zinc toxicity? Neurology. 2000; 54: 1705–1706.
Hedera P, Fink JK, Bockenstedt PL, Brewer GJ. Myelopolyneuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown origin: further support for existence of a new zinc overload syndrome. Arch Neurol. 2003; 60: 1303–1306.
Williams DM. Copper deficiency in humans. Semin Hematol. 1983; 20: 118–128.
Al-Rashid RA, Spangler J. Neonatal copper deficiency. N Engl J Med. 1971; 285: 841–843.
Prasad AS, Brewer GJ, Schoomaker EB, Rabbani P. Hypocupremia induced by zinc therapy in adults. JAMA. 1978; 240: 2166–2168.
Karpel JT, Peden VH. Copper deficiency in long-term parenteral nutrition. J Pediatr. 1972; 80: 32–36.
Smith JC, Zeller JA, Brown ED, Ong SC. Elevated plasma zinc: a heritable anomaly. Science. 1976; 193: 496–498.
Prasad AS, Ortega J, Brewer GJ. Trace elements in sickle cell disease. JAMA. 1976; 235: 2396–2398.
Prasad AS. Zinc in human nutrition. Crit Rev Clin Lab Sci. 1977; 8: 1–80.
Van Campen DF, Mitchell EA. Absorption of Cu64, Zn65, Mo99, and Fe59 from ligated segments of the rat gastrointestinal tract. J Nutr. 1965; 86: 120–124.
Crampton RF, Matthews DM, Poisner F. Observations of the mechanism of absorption of copper by the small intestine. J Physiol. 1965; 178: 111–126.
Staël von Holstein C, Ibrahimbegovic E, Walthner B, Åkesson B. Nutrient intake and biochemical markers of nutritional status during long-term follow-up after total and partial gastrectomy. Eur J Clin Nutr. 1991; 46: 265–272.
Hayton BA, Broome HE, Lilenbaum RC. Copper deficiency-induced anemia and neutropenia secondary to intestinal malabsorption. Am J Hematol. 1995; 48: 45–47.
Valentine JS, Gralla EB. Delivering copper inside yeast and human cells. Science. 1997; 278: 817–818.

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Published In

Volume 63Number 1July 13, 2004
Pages: 33-39
PubMed: 15249607

Publication History

Received: February 5, 2004
Accepted: March 10, 2004
Published online: July 12, 2004
Published in print: July 13, 2004


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Affiliations & Disclosures

Neeraj Kumar, MD
From the Department of Neurology (Drs. Kumar and Ahlskog) and Division of Gastroenterology and Hepatology (Dr. Gross), Department of Medicine, Mayo Clinic, Rochester, MN.
John B. Gross, Jr., MD
From the Department of Neurology (Drs. Kumar and Ahlskog) and Division of Gastroenterology and Hepatology (Dr. Gross), Department of Medicine, Mayo Clinic, Rochester, MN.
J. Eric Ahlskog, PhD MD
From the Department of Neurology (Drs. Kumar and Ahlskog) and Division of Gastroenterology and Hepatology (Dr. Gross), Department of Medicine, Mayo Clinic, Rochester, MN.


Address correspondence and reprint requests to Dr. N. Kumar, 200 First Street, SW, Rochester, MN 55905; e-mail: [email protected]

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