Hostname: page-component-f554764f5-68cz6 Total loading time: 0 Render date: 2025-04-10T17:01:46.823Z Has data issue: false hasContentIssue false
  • English
  • Français

Friedreich’s Disease 1982: Etiologic Hypotheses A personal analysis

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 Avenue West, Montreal, Quebec, Canada, H2W 1R7
Rights & Permissions [Opens in a new window]

Summary:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The author reviews the arguments for and against the four etiologic hypotheses in Friedreich’s disease that have been proposed since 1974: the “pyruvate hypothesis”, the “lipidmembrane hypothesis”, the “energy-defect hypothesis” and finally the “taurine hypothesis”. While none of these hypotheses are mutually exclusive, the author shows that all of these mechanisms play some role in the pathophysiology of the symptoms, but that only the “taurine hypothesis” appears to be compatible with all the known facts and the biochemical abnormalities reported. The author proposes that a taurine retention defect (possibly due to a block in the high affinity-low capacity transport of taurine – The TH System) is a primary event in Friedreich’s disease. Whether it is the primary genetic event still has to be determined.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 9 , Issue 2 , May 1982 , pp. 243 - 263
Copyright
Copyright © Canadian Neurological Sciences Federation 1982

References

REFERENCES

Barbeau, A. (1976). Friedreich’s Ataxia 1976 – An overview. Can. J. Neurol. Sci. 3: 389–397.CrossRefGoogle ScholarPubMed
Barbeau, A. (1978). Friedreich’s Ataxia 1978 – An overview. Can. J. Neurol. Sci. 5: 161–165.CrossRefGoogle ScholarPubMed
Barbeau, A. (1979). Friedreich’s Ataxia 1979 – An overview. Can. J. Neurol. Sci. 6: 311–319.CrossRefGoogle ScholarPubMed
Barbeau, A. (1980). Friedreich’s Ataxia 1980 – An overview of the physiopathology. Can. J. Neurol. Sci. 7: 455–468.CrossRefGoogle ScholarPubMed
Barbeau, A., Charbonneau, M. and Cloutier, T. (1980). Leukocyte glutamate dehydrogenase activity in various hereditary ataxias. Can. J. Neurol. Sci. 7: 421–424.CrossRefGoogle ScholarPubMed
Barbeau, A. and Donaldson, J. (1974). Zinc, taurine and epilepsy. Arch. Neurol. 30: 52–58.Google Scholar
Barbeau, A. and Huxtable, R.J. (1978). Taurine and Neurological Disorders. Raven Press, New York.CrossRefGoogle Scholar
Barbeau, A., Inoue, N., Tsukada, Y. and Butterworth, R.F. (1975). The neuropharmacology of Taurine. Life Sci. 17: 669–677.CrossRefGoogle ScholarPubMed
Baker, H. and Frank, O. (1965). Panothenic acid, in Clinical Vitaminology. Methods and Interpretation, pp. 54–63.Google Scholar
Bassen, F.A. and Kornzweig, A.L. (1950). Malformation of the erythocytes in a case of atypical retinitis pigmentosa. Blood 5: 381–386.CrossRefGoogle Scholar
Bayoumi, R.A. and Rosalki, S.B. (1976). Evaluation of methods of coenzyme activation of erythrocyte enzymes for detection of deficiency of Vitamins B1, B2 and B6. Clin. Chem. 22: 327–335.CrossRefGoogle ScholarPubMed
Brdiczka, D. and Pette, D. (1971). Intra and extramitochondrial isozymes of (NADP) malate dehydrogenase. Eur. J. Biochem. 19: 546–551.CrossRefGoogle ScholarPubMed
Butterfield, D.A. and Markesbury, W.R. (1980). Specificity of biophysical and biochemical alterations in erythrocyte membranes in neurological disorders – Huntington’s Disease, Friedreich’s ataxia, Alzheimer’s Disease, amyotrophic lateral sclerosis, and myotonic and Duchenne muscular dystrophy. J. Neurol. Sci. 47: 261–271.CrossRefGoogle ScholarPubMed
Butterworth, R.F., Hamel, E., Landreville, F. and Barbeau, A. (1979). Amino acid changes in thiamine-deficient encephalopathy: some implications for the pathogenesis of Friedreich’s Ataxia. Can. J. Neurol. Sci. 6: 217–222.CrossRefGoogle ScholarPubMed
Butterworth, R.F., Shapcott, D., Melancon, S., Breton, G., Geoffroy, G., Lemieux, B. and Barbeau, A. (1976). Clinical laboratory findings in Friedreich’s ataxia. Can. J. Neurol. Sci. 3: 355–359.CrossRefGoogle ScholarPubMed
Carreau, J.P., Lapous, D. and Raulin, J. (1977). Signification des acides gras essentiels dans le métabolisme intermédiaire. Hypothèses sur la synthèse de l’acide lipoique. Biochimie 59: 487–496.CrossRefGoogle Scholar
Cohen, P.T. and Omenn, G.S. (1972). Human malic enzyme: high frequency polymorphism of the mitochondrial form. Biochem. Genet. 7: 303–311.CrossRefGoogle ScholarPubMed
Constantopoulos, G., Chang, C.S. and Barranger, J.A. (1980). Normal pyruvate dehydrogenase complex activity in patients with Friedreich’s ataxia. Ann. Neurol. 8: 636–639.Google Scholar
Darsee, J.R. and Heymsfield, S.R. (1981). Decreased myocardial taurine levels and hypertaurinuria in a kindred with mitralvalve prolapse and congestive myopathy. New Engl. J. Med. 304: 129–135.CrossRefGoogle Scholar
Davignon, J., Huang, Y.S., Wolf, J.P. and Barbeau, A. (1979). Fatty acid profile of major lipid classes in plasma lipoproteins of patients with Friedreich’s ataxia – Demonstration of a low linoleic acid content most evident in the cholesterol-ester fraction. Can. J. Neurol. Sci. 6: 275–283.CrossRefGoogle ScholarPubMed
Elias, E., Muller, D.P.R. and Scott, J. (1981). Association of spino-cerebellar disorders with cystic fibrosis on chronic childhood cholestasis and very low serum vitamin E. The Lancet 2: 1319–1321.CrossRefGoogle Scholar
Evans, O.B. (1981). Normal muscle pyruvate oxidation in spino-cerebellar degenerations. Ann. Neurol. 9: 93–94.CrossRefGoogle Scholar
Filla, A., Butterworth, R.F. and Barbeau, A. (1979). Pilot studies on membranes and some transport mechanisms in Friedreich’s ataxia. Can. J. Neurol. Sci. 6: 285–289.CrossRefGoogle ScholarPubMed
Filla, A., Butterworth, R.F., Geoffroy, G., Lemieux, B. and Barbeau, A. (1978). Platelet taurine uptake in spinocerebellar degeneration. Can. J. Neurol. Sci. 5: 119–123.CrossRefGoogle ScholarPubMed
Filla, A., Postiglione, A., Rubba, P., Patti, L., De Michele, G., Palma, V., Brescia Morra, V. and Campanella, G. (1980). Plasma lipoprotein concentration and erythrocyte membrane lipids in patients with Friedreich’s ataxia. Acta Neurol. NS2: 382–389.Google ScholarPubMed
Frenkel, R. and Cobo-Frenkel, A. (1973). Differential characteristics of the cytosol and mitochondrial isozymes of malic enzyme from bovine brain – Effects of dicarboxylic and sulfhydryl reagents. Archs. Biochem. Biophys. 158: 323–330.CrossRefGoogle ScholarPubMed
Geoffroy, G., Barbeau, A., Breton, G., Lemieux, B., Aube, M., Leger, C. and Bouchard, J.P. (1976). Clinical description and Roentgenologic evaluation of patients with Friedreich’s ataxia. Can. J. Neurol. Sci. 3: 279–386.CrossRefGoogle ScholarPubMed
Goldberg, A.L. and Odessey, R. (1972). Oxidation of amino acids by diaphragm from fed and fasted rats. Am. J. Physiol. 223: 1384–1391.CrossRefGoogle ScholarPubMed
Goodman, H.O., Connoly, B.M., Mclean, W. and Resnick, M. (1980) Taurine transport in epilepsy. Clin. Chem. 26: 414–419.CrossRefGoogle ScholarPubMed
Greenfield, J.G. (1954). The spinocerebellar degenerations. Blackwell Scientific Publications. Oxford.Google Scholar
Henderson, N.S. (1966). Isozymes and genetic control of NADP-malate dehydrogenase in mice. Archs. Biochem. Biophys. 117: 28–33.CrossRefGoogle ScholarPubMed
Huang, Y.S., Cunnane, S.C., Horrobin, D.F. and Davignon, J. (1982). Most biological effects of zinc deficiency corrected by γ-linolenic acid (18:3w6) but not by linoleic acid (18:2w6). Atherosclerosis 41: 193–207.CrossRefGoogle Scholar
Huang, Y.S., Marcel, Y.L., Vezina, C., Barbeau, A. and Davignon, J. (1980). Lecithin: cholesterol acyltransferase activity and fatty acid composition of erythrocyte phospholipids in Friedreich’s ataxia. Can. J. Neurol. Sci. 7: 429–434.CrossRefGoogle ScholarPubMed
Huang, Y.S., Nestruck, A.C., Barbeau, A., Bouchard, J.P. and Davignon, J. (1978). Plasma lipids and lipoproteins in Friedreich’s ataxia and familial spastic ataxia – Evidence for an abnormal composition of high density lipoproteins. Can. J. Neurol. Sci. 5: 149–156.CrossRefGoogle ScholarPubMed
Huxtable, R.J., Azari, J., Relsine, T., Johnson, P., Yamahura, H.I. and Barbeau, A. (1979). Regional distribution of amino acids in Friedreich’s ataxia brains. Can. J. Neurol. Sci. 6: 255–258.CrossRefGoogle ScholarPubMed
Huxtable, R.J. and Barbeau, A. (1976) Editors. Taurine. Raven Press, New York.Google Scholar
Huxtable, R.J. and Pasantes-Morales, H. (1982). Editors. Taurine in Nutrition and Neurology. Adv. Exp. Med. Biol. Vol. 139, Plenum Press, N.Y.CrossRefGoogle Scholar
Jacobsen, J.G. and Smith, L.H. (1968). Biochemistry and physiology of taurine and taurine derivatives. Physiol. Reviews 48: 424–511.CrossRefGoogle ScholarPubMed
Kark, R.A.P., Blass, J.P. and Engel, W.K. (1974). Pyruvate oxidation in neuromuscular disease – Evidence for a genetic defect in two families with the clinical syndrome of Friedreich’s ataxia. Neurology 24: 964–971.CrossRefGoogle ScholarPubMed
Kark, R.A.P., and Rodriguez-Bud-Elli, M.M. (1979). Clinical correlations of partial deficiency of lipoamide dehydrogenase. Neurology 29: 1006–1013.CrossRefGoogle ScholarPubMed
Kark, R.A.P. and Rodriguez-Budelli, M.M. (1979). Pyruvate dehydrogenase deficiency in spino-cerebellar degenerations. Neurology 29: 126–131.CrossRefGoogle Scholar
Kark, R.A.P., Rodriguez-Budelli, M., Perlman, S., Guelley, W.F. and Torok, K. (1980). Preclinical diagnosis and carrier detection in ataxia associated with abnormalities of lipoamide dehydrogenase. Neurology 30: 502–508.CrossRefGoogle ScholarPubMed
Landriscina, C, Megli, F.M. and Quagliariello, E. (1976). Turnover of fatty acids in rat liver cardiolipin: comparison with other mitochondrial phospholipids. Lipids 11: 61–65.CrossRefGoogle ScholarPubMed
Launa Y, M., Lapous, D. and Raulin, J. (1981). Control of replication by dietary lipids and namely by linoleic acid in liver and adipose tissue of developing rats. Prog. Lipid. Res. 20: 331–338.CrossRefGoogle Scholar
Lee, S.H. and Davis, E.J. (1979). Carboxylation and decarboxylation reactions – Anaplerotic flux and removal of citrate cycle intermediates in skeletal muscle. J. Biol. Chem. 254: 420–430.CrossRefGoogle ScholarPubMed
Lemieux, B., Barbeau, A., Beroniade, V., Shapcott, D., Breton, G., Geoffroy, G. and Melancon, S. (1976). Amino acid metabolism in Friedreich’s ataxia. Can. J. Neurol. Sci. 3: 373–378.CrossRefGoogle ScholarPubMed
Lin, R.C. and Davis, E.J. (1974). Malic enzyme of rabbit heart mitochondria. J. Biol. Chem. 249: 3867–3875.CrossRefGoogle ScholarPubMed
Livingstone, I.R., Mastaglia, F.L., Pennington, R.J.T. (1980). An investigation of pyruvate metabolism in patients with cerebellar and spino-cerebellar degeneration. J. Neurol. Sci. 48: 123–132.CrossRefGoogle Scholar
Lombardini, J.B. (1975). An enzymatic derivative double-isotope assay for measuring tissue levels of taurine. J. Pharmacol. Exp. Ther. 193: 301–308.Google ScholarPubMed
Lubozynski, M.F. and Roelofs, R.I. (1975). Friedreich’s ataxia: a review of recent literature. South. Med. J. 68: 757–763.CrossRefGoogle Scholar
Melancon, S.B., Grignon, B., Ledru, E., Geoffroy, G., Potier, M., Dallaire, L. and Vanasse, M. (1980). The beta-amino acid transport system in Friedreich’s ataxia. Can. J. Neurol. Sci. 7: 441–446.CrossRefGoogle ScholarPubMed
Morgan, R.O., Naglie, G., Horrobin, D.F. and Barbeau, A. (1979). Erythrocyte protoporphyrin levels in patients with Friedreich’s and other ataxias. Can. J. Neurol. Sci. 6: 227–232.CrossRefGoogle ScholarPubMed
Perry, T.L., Hansen, S., Currier, R.D. and Berry, K. (1978). Abnormalities in neurotransmitter amino acids in dominantly inherited cerebellar disorders. Adv. Neurol. 21: 303–314.Google ScholarPubMed
Purkiss, P., Baraitser, M., Borud, O. and Chalmers, R.A. (1981). Biochemical and clinical studies of Friedreich’s ataxia. J. Neurol. Neurosurg. Psych. 44: 574–580.CrossRefGoogle ScholarPubMed
Reed, L.J. (1974). Multienzyme complexes. Accounts of chemical Research 7: 40–46.CrossRefGoogle Scholar
Refsum, S. (1946). Heredopathia atactica polyneuritiformis: a familial syndrome not hither to described. A contribution to the clinical study of the hereditary diseases of the nervous system. Acta psychiat. Scand. Suppl. 38: 1–303.Google Scholar
Robinson, N. (1968). Chemical changes in spinal cord in Friedreich’s ataxia and motor neurone disease. J. Neurol. Neurosurg. Psych. 31: 330–333.CrossRefGoogle ScholarPubMed
Rodriguez-Budelli, M. and Kark, R.A.P. (1978). Kinetic evidence for a structural abnormality of lipoamide dehydrogenase in two patients with Friedreich’s ataxia. Neurology 28: 1283–1286.CrossRefGoogle Scholar
Sauer, L.A., Dauchy, R.T. and Nagel, W.O. (1979). Identification of a NAD(P)+ -Dependent ‘Malic’ enzyme in small intestinal-mucosal mitochondria. Biochem. J. 184: 185–188.CrossRefGoogle ScholarPubMed
Siddiquit, U.A., Goldflam, T. and Goodridge, A.G. (1981). Nutritional and hormonal regulation of the translatable levels of malic enzyme and albumin mRNA in avian liver cells in vivo and in culture. J. Biol. Chem. 256: 4544–4550.CrossRefGoogle Scholar
Simpson, E.R. and Estabrook, R.W. (1969). Mitochondrial malic enzyme: the source of reduced nicotinamide adenine dinucleotide phosphate for steroid hydroxylation in bovine adrenal cortex mitochondria. Archs Biochem. Biophys. 129: 384–395.CrossRefGoogle ScholarPubMed
Simpson, D.M. and Poulson, R. (1977). Effects of lipids on the activity of ferrochelatase. Biochem. Biophys. Acta 482: 461–469.Google ScholarPubMed
Spencer, P.S., Sabri, M.I., Schaumburg, H.H. and Moore, C.L. (1979). Does a defect of energy metabolism in the nerve fiber underlie axonal degeneration in polyneuropathies? Ann. Neurol. 5: 501–507.CrossRefGoogle ScholarPubMed
Stumpf, D.A., Mccabe, E.R.B., Parks, J.K., Bullen, W.W. and Schiff, S. (1979). Loosely coupled mitochondrial oxidative phosphorylation induced by protoporphyrin. Biochem. Med. 21: 182–189.CrossRefGoogle ScholarPubMed
Stumpf, D., Parks, J., Eguren, L. and Haas, R. (1981). Mitochondrial malic enzyme deficiency in Friedreich’s ataxia. Ann. Neurol. 10: 283.Google Scholar
Stumpf, D.A., Parks, J.K., Eguren, L.A. and Haas, R. (1982). Friedreich’s ataxia: III – Mitochondrial malic enzyme deficiency. Neurology(Ny) 32: 221–227.CrossRefGoogle ScholarPubMed
Swierczynski, J. (1980). Purification and some properties of extramitochondrial malic enzyme from rat skeletal muscle. Biochem. Biophys. Acta. 616: 10–21.Google ScholarPubMed
Thoren, C. (1962). Diabetes mellitus in Friedreich’s ataxia. Acta Paediat. 51 (suppl. 135): 239–247.CrossRefGoogle Scholar
Thurston, J.H., Hauhart, R.E. and Naccarato, E.F. (1981). Taurine: possible role in osmotic regulation of mammalian heart. Science 214: 1373–1374.CrossRefGoogle ScholarPubMed
Tolis, G., Menta, A., Harvey, C., Andermann, E., Andermann, F. and Barbeau, A. (1980). Friedreich’s ataxia and glucose tolerance: 1. the effect of ingested glucose on serum glucose and insulin values in homozygotes, obligate heterozygotes and potential carriers of the Friedreich’s ataxia gene. Can. J. Neurol. Sci. 7: 397–400.CrossRefGoogle Scholar
Tyrer, J.H. (1975). Friedreich’s ataxia. Handbook of clinical neurology, vol. 21: 319–364. Vinken, P.J. and Bruyn, G.W., Editors, North-Holland Publishing Co. Amsterdam.Google Scholar
Walker, J.L., Chamberlain, S. and Robinson, N. (1980). Lipids and lipoproteins in Friedreich’s ataxia. J. Neurol. Neurosurg. Psychiat. 43: 111–117.CrossRefGoogle ScholarPubMed
Yao, J.K. and Dyck, P.J. (1978). Lipid abnormalities in hereditary neuropathy. Part 2: serum phospholipids. J. Neurol. Sci. 36. 225–236.CrossRefGoogle ScholarPubMed
Yao, J.K. and Dyck, P.J. (1979). Accumulation of polyunsaturated fatty acids in developing peripheral nerve. Proc. Amer. Society Neurochem. 12: 214.Google Scholar