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Erythrocyte Protoporphyrin Levels in Patients with Friedreich's and other Ataxias

Published online by Cambridge University Press:  18 September 2015

R.O. Morgan ,
G. Naglie ,
D.F. Horrobin  and
A. Barbeau
R.O. Morgan
Affiliation:
Clinical Research Institute of Montreal
G. Naglie
Affiliation:
Clinical Research Institute of Montreal
D.F. Horrobin
Affiliation:
Clinical Research Institute of Montreal
A. Barbeau
Affiliation:
Clinical Research Institute of Montreal
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Of 13 patients with Fried-reich's ataxia (Type la) and 17 with type Ila recessive ataxias, all were found to have levels of “free erythrocyte protoporphyrin “ (FEP) above the normal range. The rise in FEP in Friedreich's ataxia correlated well with the age of the individual and thus appears to be related to the course of the disease. Subjects with olivo-ponto-cerebel-lar atrophy, Charlevoix syndrome, Duchenne muscular dystrophy, and Parkinson's disease were also found to have significantly elevated FEP, although the distribution overlapped with the normal range.

The finding of elevated FEP may indicate a relative heme deficiency in ataxia due to inhibition offerrochelatase leading to a state of ineffective, persistent erythropoiesis. The possibility of a prosta-glandin abnormality being related to this defect and to the pathogenesis of ataxia is considered.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 6 , Issue 2 , May 1979 , pp. 227 - 232
Copyright
Copyright © Canadian Neurological Sciences Federation 1979

References

Allen, S. H. (1956) Effects of vitamin B12 deficiency and of copper deficiency on the concentration of free protoporphyrin in the erythrocytes of sheep. Biochem. J. 63: 461–469.Google ScholarPubMed
Anderson, K. E.Sassa, S., Peterson, C. M. and Kappas, A. (1977). Increased erythrocyte uroporphyrinogen-1-synthetase, delta-aminolevulinic acid dehydratase and protoporphyrin in hemoly-tic anemieas. Amer. J. Med. 63: 359–364.Google Scholar
Barbeau, A., Breton, G., Lemieux, B., Butterworth, R. F. (1976). Bilirubin metabolism — preliminary investigation. Can. J. Neurol. Sci. 3: 365–372.Google ScholarPubMed
Chou, A. C., Broun, G. O. and Fitch, C. D. (1978). Abnormalities of iron metabolism and erythropoiesis in vitamin E-deficient rabbits. Blood 52: 187–195.Google ScholarPubMed
Dematteis, F., Abbritti, G. and Gibbs, A. H. (1973). Decreased liver porphyrin-metal chelatase in hepatic porphyria caused by 3,5-diethoxycarbonyl-l,4-dihydrocolli-dine. Biochem. J. 134: 717–727.Google Scholar
Dukes, P. P., Shore, N. A., Hammond, G. D. and Ortega, J. A. (1975). Prostaglandins and erythropoietin action. In Nakao, K. et al (eds), Univ. Park Press, Baltimore, 1975, pp 3–14.Google Scholar
Fischl, J. and Rabiah, S. (1964). Determination of free and total indole-3-acetic acid and of the indole index. Clin. Chem. 10: 281–290.Google ScholarPubMed
Gibbard, S. and Schoental, R. (1977). Effect of nicotinamide on development and localization of tumors, and on excretion of porphyrins in urine of rats given hepatocar-cinogen, diethylnitrosamine. Brit. J. Cancer 35: 254.Google Scholar
Goldberg, A. (1959). Acute intermittent porphyria. A study of 50 cases. Quart. J. Med. 28: 183–209.Google ScholarPubMed
Granick, S., Sassa, S., Granick, J. L., Levere, R. D. and Kappas, A. (1972). Assays for porphyrins, delta-aminolevulinic acid dehydratase, and uroporphyrinogen synthetase in micoliter samples of whole blood: Applications to metabolic defects involving the heme pathway. Proc. Nat. Acad. Sci. (U.S.A.) 69: 2381–2385.Google Scholar
Hamel, E., Bedard, D., Laviolette, F., Butterworth, R. F. and Barbeau, A. (1978). Familial hyperbilirubinemia in Friedreich's ataxia. Can. J. Neurol. Sci. 5: 101–104.Google ScholarPubMed
Hemler, M., Lands, W. E. M. and Smith, W. L. (1976). Purification of the cyclooxygenase that forms prostaglandins. Demonstration of two forms of iron in the holoenzyme. J. Biol. Chem. 251: 5575–5579.Google ScholarPubMed
Horrobin, D. F. (1978) Prostaglandins: Physiology, Pharmacology and Clinical Significance. Eden Press, Montreal, 1978, pp. 259.Google Scholar
Howell, J. McC. and Thompson, J. N. (1967). Lesions associated with the development of ataxia in vitamin A-deficient chicks. Brit. J. Nutr. 21: 741–750.Google ScholarPubMed
Johnson, L. W. and Schwartz, S.. (1972). Relation of porphyrin content to red cell age: analysis by fractional hemolysis. Proc. Soc. Exp. Biol. Med. 139: 191–197.Google ScholarPubMed
Krammer, A., Cartwright, G. E. and Wintrobe, M. M. (1954). The anemia of infection. XIX. Studies on free erythrocyte coproporphyrin and protoporphyrin. Blood 9: 183–188.Google ScholarPubMed
Labbe, R. F. and Nielsen, L. (1976). Clinical-biochemical interpretations of erythrocyte protoporphyrin. Ferrochelatase-pyridoxal phosphate studies. In Porphyrins in Human Diseases, First Inťl Porphyrin Meeting, Freiburg, 1975, Karger, Basel, 1976, pp. 141–147.Google Scholar
Liem, H. H., Miyai, K. and Muller — Eberhard, U.. (1977). Effect of porphyrino-genic agents on protein synthesis and bilirubin formation by the isolated perfused rat liver. Biochim. Biophys. Acta 496: 52–64.Google ScholarPubMed
Mathews-Roth, M., Pathak, M., Fitzpatrick, T., Harber, L. and Kasse, E.. (1974). Beta-carotene as an oral photoprotective agent in erythropoietic protoporphyria. J. Amer. Med. Ass. -28: 1004–1008.Google ScholarPubMed
Mertin, J. and Meade, C. J. (1977). Relevance of fatty acids in multiple sclerosis. Br. Med. Bull. 33: 67–71.Google ScholarPubMed
Moncada, S., Bunting, S., Mullane, K., Thorogood, P., Vane, J. R., Raz, A. and Needleman, P.. (1977). Imidazole-selective inhibitor of thrombox-ane synthetase. Prostaglandins 13: 611–618.Google Scholar
Orfanos, A. P., Murphy, W. H. and Guthma, R. (1977). A simple fluorometric assay of protoporphyrin in erythrocytes as a screening test for lead poisoning. J. Lab. Clin. Med. 89: 659–665.Google ScholarPubMed
Perry, T. L., Maclean, J., Perry, T. L. and Hansen, S. (1976). Effect of 3-acetylpyridine on putative neurotransmitter amino acids in rat cerebellum. Brain Res. 109: 632–635.Google ScholarPubMed
Pinelli, A. and Favall, L. (1972), Antili-paemic and antiporphyric activity of nicotinic acid in allylisopropylacetamide-treated rats. Biochim. Biophys. Acta 279: 316–319.Google ScholarPubMed
Sassa, S., Granick, S., Bickers, D. R., Bradlow, H. L. and Kappas, A. (1974). A microassay for uroporphyrinogen 1 synthase, one of three abnormal enzyme activities in acute intermittant porphyria, and its application to the study of the genetics of this disease. Proc. Nat. Acad. Sci. (U.S.A.) 71: 732–736.Google Scholar
Sassa, S., Granick, S. and Kappas, A. (1975). Effect of lead and genetic factors on heme biosynthesis in the human red cell. Ann. N. Y. Acad. Sci. 244: 419–440.Google ScholarPubMed
Shimamoto, T., Takashima, Y., Kobayashi, M., Moriya, K. and Takahashi, T. (1976). A specific throm-boxane A2-antagonistic effect of pyridinol-carbamate and phthalazinol. Proc. Jap. Acad. 52: 591–594.Google Scholar
Simpson, D. M. and Poulson, R. (1977). Effects of lipids on the activity of ferrochela-tase. Biochim. Biophys. Acta 482: 461–469.Google Scholar
Smith, R. M., Osborne-White, W. S. and O'Dell, B. L. (1976). Cytochromes in brain mitochondria from lambs with enzootic ataxia. J. Neurochem. 26: 1145–1148.Google ScholarPubMed
Szanto, J. and Gallyas, F. (1966). A study of iron metabolism in neuro-psychiatric patients. Hallervorden-Spatz disease. Arch. Neurol. 14: 438–442.Google Scholar
Trapp, B. D. and Bernsohn, J. (1978). Essential fatty acid deficiency and CNS myelin — Biochemical and morphological observations. J. Neurol. Sci. 37: 249–266.Google ScholarPubMed
Vincent, J. E. and Zijlstra, F. J. (1978). Nicotinic acid inhibits thromboxane synthesis in rat platelets. 7th Inťl Congress of Pharmacology, Paris, 1978, Abstract # 2012, pp 628.Google Scholar
Wagner, G. S., Dinamarca, M. L. and Tephly, T. R. (1976). Studies on ferrochelatase activity: Role in regulation of hepatic heme biosynthesis. In Porphyrins in Human Diseases, First Inťl Porphyrin Meeting, Freiburg, 1975, Karger, Basel, 1976, pp 111–122.Google Scholar
Wennmalm, A. (1977). Nicotine stimulates prostaglandin formation in the rabbit heart. Br. J. Pharmacol. 59: 95–100.Google ScholarPubMed