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Friedreich's Ataxia 1980 An Overview of the Physiopathology

Published online by Cambridge University Press:  18 September 2015

André Barbeau
André Barbeau*
Affiliation:
Department of Neurobiology, Clinical Research Institute of Montreal
*
Clinical Research Institute of Montreal, 110 Pine West Ave., Montreal, Quebec, Canada H2W 1R7
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Phase three of the Quebec Cooperative Study of Friedreich's Ataxia was devoted to an understanding of the physiopathology of individual symptoms on the basis of previously discovered biochemical leads. The present paper attempts to pull these results together by presenting, as a hypothesis, a unifying scheme of possible interactions and relationships. The central core of this hypothesis is the demonstration in Friedreich's ataxia of a state of mitochondrial energy deprivation. This is indirectly responsible for such associated and important symptoms as muscle weakness, dying-back neuropathy, scoliosis and hypertrophic cardiomyopathy. Secondarily, and possibly as an independent but linkedevent, the entry of glucose into cells and pyruvate oxidation, are slowed down, favoring the development of diabetes. As a consequence, tissue concentrations of glutamic acid and aspartic acid are decreased, particularly in more vulnerable areas such as the cerebellum, brain stem and dorsal root ganglia. This tissue deficiency in putative excitatory neurotransmitters is directly responsible for the symptom of ataxia. This conclusion is reinforced by the correction of the ataxia in glutaexperimental animals, by the intraventricular injection of the same amino acids, and not by the injection of other stimulants of motricity. The observed mitochondrial energy deprivation could be the metabolic consequence of major changes in the linoleic acid (18:2) composition of inner mitochondrial membrane phospholipids, such as cardiolipin. Such decreases in membrane 18:2 could be the result of interference with the normal incorporation of this fatty acid to lipoproteins and/or cell membranes. It is at this level that the search for the specific enzyme defect in Friedreich's ataxia is continuing.

Type
Quebec Cooperative Study of Friedreich's Ataxia
Information
Canadian Journal of Neurological Sciences , Volume 7 , Issue 4 , November 1980 , pp. 455 - 468
Copyright
Copyright © Canadian Neurological Sciences Federation 1980

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