Copper deficiency mistaken for ALS.

[Bill-ut]

I copied the following from the ALSTDF Forum.

http://www.als.net/forum/active.asp

Copper deficiency mistaken for ALS.
Posted on: 12/04/2006 17:58:41
Message:

This just appeared in the December print edition issue of the journal:

Case of the Month
Motor neuron disease associated with copper deficiency
Conrad C. Weihl, MD, PhD, Glenn Lopate, MD *
Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA
email: Glenn Lopate (lopateg@neuro.wustl.edu)
*Correspondence to Glenn Lopate, Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA

Funded by:
NIH; Grant Number: 5K08AG026271
Washington University Neuromuscular Research Fund

Keywords
amyotrophic lateral sclerosis • copper deficiency • motor neuron disease • myelodysplastic syndrome • myelopathy • spinal cord disease

Abstract
Copper deficiency in humans is a rare cause of myeloneuropathy that usually presents with a spastic ataxic gait, hyperreflexia, and distal sensory loss similar to that seen in patients with subacute combined degeneration. We describe three copper-deficient patients, two of whom were referred with a presumptive diagnosis of amyotrophic lateral sclerosis, who had progressive asymmetric weakness or electrodiagnostic findings of proximal and distal denervation suggestive of lower motor neuron disease. Copper replacement resulted in stabilization or mild improvement in weakness. The clinical spectrum of human copper deficiency should include lower motor neuron disease in addition to a syndrome of spastic ataxia. Muscle Nerve, 2006
Accepted: 29 June 2006

I have the full text and would post it here but I don't have reprint permission. The article said that 3 mg. of copper gluconate per day for a few months stabilized the patient.

The authors don't know exactly what role the copper plays in neurodegeneration but all of their copper deficient patients were anemic. It has long been known that copper is necessary for processing iron. I have written about how anemia can cause neurodegeneration and my work has recently been discovered by neuroscientists at the NIH who have proposed a collaboration with me. In fact, it was Sharon Cooperman, MD, PhD of the NIH who alerted me to this research.

[Proton Soup]

Med Hypotheses. 2008;71(2):229-36. Epub 2008 May 9.Click here to read Links
Copper deficiency myelopathy and subacute combined degeneration of the cord - Why is the phenotype so similar?
Winston GP, Jaiser SR.

National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.

Copper deficiency myelopathy (CDM) is an increasingly recognised mimic of subacute combined degeneration (SCD) of the cord due to cobalamin (vitamin B(12)) deficiency. It has been suggested that copper deficiency induces myelopathy through dysfunction of cytochrome oxidase, which is known to be copper-dependent. However, cytochrome oxidase is not cobalamin-dependent, so this hypothesis fails to explain the phenotypic similarity between CDM and SCD. We propose that the first step in a final common pathway of CDM and SCD is dysfunction of the methylation cycle. This cycle includes both copper and cobalamin-dependent enzymes and catalyses the net transfer of a methyl group from methyltetrahydrofolate to a variety of macromolecules, including myelin proteins. Dysfunction of the cycle might therefore cause failure of myelin maintenance and ultimately myelopathy. One step of the methylation cycle is catalysed by methionine synthase, which is known to be cobalamin-dependent. Nitrous oxide specifically inhibits this enzyme by inactivating methylcobalamin, causing SCD in animals and humans. Both animal and human data suggest that methionine synthase also requires copper, implying that the enzyme may be involved in the pathogenesis of CDM. Another enzyme involved in the methylation cycle, S-adenosylhomocysteine hydrolase, may be regulated by copper. Although this enzyme is not cobalamin-dependent, its potential impairment in copper deficiency may contribute to the overall dysfunction of the methylation cycle. In cases of congenital deficiencies of methylation cycle enzymes, spinal and cerebral demyelination was observed, providing further support for a critical role of the methylation cycle in myelination. Biochemical dysfunction of the methylation cycle has been reported in HIV myelopathy, which has pathological parallels with SCD. This raises the possibility that other demyelinating myelopathies might involve an impairment of the methylation cycle. Our hypothesis could be tested by measuring CSF concentrations of methylation cycle intermediates in cases of CDM, as these reflect spinal cord tissue levels. If it were confirmed, the hypothesis would not only provide a plausible explanation for the phenotypic similarity between CDM and SCD, but might also open up further therapeutic options such as methionine and betaine supplementation.

PMID: 18472229 [PubMed - in process