Summary
A 9-year study of thiamine metabolism and cellular transport was performed in two patients with thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and sensorineural deafness, in their relatives, and in age-matched controls from the same area. The ratios between the content of thiamine and that of its phosphoesters in erythrocytes were within the normal range, whereas the absolute values of thiamine and thiamine compounds were reduced by about 40% as compared to controls. Thiamine pyrophosphokinase activity was about 30% lower than in controls. Thiamine treatment restored the levels of thiamine and thiamine compounds to normal values, whereas kinase was unaffected. Both the saturable (specific, predominant at low, < 2 µmol/L, physiological concentrations of thiamine) and the non-saturable component of thiamine transport were investigated. Erythrocytes and ghosts from patients exhibited no saturable component, this abnormality being specific for the patients and not shared by their parents. It is concluded that the cells from thiamine-responsive megaloblastic anaemia patients contain low levels of thiamine compounds, probably due to their inability to take up and retain physiological concentrations of thiamine, as a result of the lack of the saturable, specific component of transport and reduced thiamine pyrophosphokinase.
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Baker, H. and Frank, O. Absorption, utilization and clinical effectiveness of allithiamines compared to water-soluble thiamines.J. Nutr. Sci. Vitaminol. 22 (suppl.) (1976) 63–68
Bettendorff, L., Grandfils, C., De Rycker, C. and Schoffeniels, E. Determination of thiamine and its phosphate esters in human blood serum at femtomole levels.J. Chromatogr. Biomed. Appl. 382 (1986) 297–302
Bötticher, B. and Bötticher, D. A new HPLC method for the simultaneous determination of B1-, B2- and B6-vitamers in serum and whole blood.Int. J. Vit. Nutr. Res. 57 (1987) 273–278
Casirola, D., Ferrari, G., Gastaldi, G., Patrini, C. and Rindi, G. Transport of thiamine by brush-border membrane vesicles from rat small intestine.J. Physiol. (London) 398 (1988) 329–339
Casirola, D., Patrini, C., Ferrari, G. and Rindi, G. Thiamin transport by human erythrocytes and ghosts.J. Membrane Biol. 118 (1990) 11–18
Cusaro, G., Rindi, G. and Sciorelli, G. Subcellular distribution of thiamine-pyrophosphokinase and thiamine-pyrophosphatase activities in rat isolated enterocytes.Int. J. Vit. Nutr. Res. 47 (1977) 99–106
De Caro, L., Rindi, G. and de Giuseppe, L. Contents in the rat tissue of thiamine and its phosphates during dietary thiamine deficiency.Int. Rev. Vit. Res. 31 (1961) 333–340
De Caro, L. G. Jr. Vitesse de conduction et contenu en thiamine (cocarboxylase) du nerf.Electroencephalogr. Clin. Neurophysiol. 14 (suppl. 22) (1962) 26–29
Deus, B. and Blum, H. Subcellular distribution of thiamine pyrophosphokinase activity in rat liver and erythrocytes.Biochim. Biophys. Acta 219 (1970) 489–492
Dunnett, C. W. New tables for multiple comparisons with a control.Biometrics 20 (1964) 482–491
Faller, A. Weitere Untersuchungen ueber den Einfluss der B1 Avitaminose auf den Inselapparat der Ratte.Schweiz. Med. Wochenschr. 89 (1959) 380
Glantz, S. A.Statistica per Discipline Biomediche, Programma Applicativo, McGraw-Hill Libri Italia, Milano, 1988
Hakim, A. M., Carpenter, S. and Pappius, H.M. Metabolic and histological reversibility of thiamine deficiency.J. Cerebr. Blood Flow Metab. 3 (1983) 468–477
Hell, D., Six, P. and Salked, R. Vitamin B1-Mangel bei chronischen Athylikern und sein klinisches Korrelat.Schweitz. Med. Wochenschr. 106 (1976) 1466–1470
Hoyumpa, A. M. Jr., Middleton, H. M. III, Wilson, F. A. and Schenker, S. Thiamine transport across the rat intestine. I. Normal characteristics.Gastroenterology 68 (1975) 1218–1227
Ida, T. Bone marrow in beriberi patients.Nippon ketsuekigakukai Zasshi 2 (1983) 439 (Cited by Inouye, K. and Katsura, E. Clinical signs and metabolism of beriberi patients. In Shimazono, N. and Katsura, E. (eds.)Review of Japanese Literature on Beriberi and Thiamine, Vitamin B Res. Committee of Japan, 1965, pp. 64–80
Komai, T., Kawai, K. and Shindo, H. Active transport of thiamine from rat small intestine.J. Nutr. Sci. Vitaminol. 20 (1974) 163–177
Laforenza, U., Patrini, C., Gastaldi, G. and Rindi, G. Effects of acute and chronic ethanol administration on thiamine metabolizing enzymes in some brain areas and in other organs of the rat.Alcohol and Alcoholism 25 (1990) 591–603
Li, C. C.Introduction to Experimental Statistics, McGraw-Hill, New York, 1964, pp. 418–423
Lonsdale, D. Hypothesis and case reports: possible thiamin deficiency.J. Am. Coll. Nutr. 9 (1990) 13–17
Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. Protein measurement with Folin phenol reagent.J. Biol. Chem. 193 (1951) 265–275
McCandless, D. W. and Schenker, S. Encephalopathy of thiamine deficiency: studies of intracerebral mechanisms.J. Clin. Invest. 47 (1968) 2268–2280
Patrini, C. and Rindi, G. An improved method for the electrophoretic separation and fluorometric determination of thiamine and its phosphates in animal tissues.Int. J. Vit. Nutr. Res. 50 (1980) 10–18
Poggi, V., Longo, B., De Vizia, B., Andria, G., Rindi, G., Patrini, C. and Cassandro, E. Thiamin-responsive megaloblastic anaemia: a disorder of thiamin transport?J. Inher. Metab. Dis. 7 (suppl. 2) (1984) 153–154
Poggi, V., Rindi, G., Patrini, C., De Vizia, B., Longo, G. and Andria, G. Studies on thiamine metabolism in thiamine-responsive megaloblastic anaemia.Eur. J. Pediatr. 148 (1989) 307–311
Rathanaswami, P. and Sundaresan, R. Effects of insulin secretagogues on the secretion of insulin during thiamine deficiency.Biochem. Int. 17 (1988) 523–528
Rinehart, J. F., Greenberg, L. D. and Ginzton, L. L. Thiamine deficiency in the Rhesus monkey.Blood 3 (1948) 1453–1459
Rinehart, J. F., Friedman, M. and Greenberg, L. D. Effect of experimental thiamin deficiency of the nervous system of the Rhesus monkey.Arch. Pathol. 48 (1949) 129–139
Sato, J. Impairment of hearing acuity related to beriberi.Nippon Jibi-inkoka-kai Kaiho 32 (1926) 302 (Cited by Inouye, K. and Katsura, E. Clinical signs and metabolism of beriberi patients. In Shimazono, N. and Katsura, E. (eds.)Review of Japanese Literature on Beriberi and Thiamine, Vitamin B Res. Committee of Japan, 1965, pp. 64–80
Schwoch, G. and Passow, H. Preparation and properties of human erythrocyte ghosts.Mol. Cell. Biochem. 2 (1973) 197–218
Shigematsu, Y., Nakai, A., Kuriyama, M., Kikawa, Y., Konishi, J., Sudo, M. and Itokawa, Y. Delayed auditory brainstem response in thiamin-deficient rats.J. Nutr. Sci. Vitaminol. 36 (1990) 209–215
Sklan, D. and Trostler, N. Site and extent of thiamin absorption in the rat.J. Nutr. 107 (1977) 353–356
Speizer, L., Haugland, R. and Kutchai, H. Asymmetric transport of a fluorescent glucose analogue by human erythrocytes.Biochim. Biophys. Acta 815 (1985) 75–84
Tenconi, F., Bertoncelli, M., Gatti, F. and Rosso, C. A novel vitamin B1 derivative: benzoyloxymethyl-thiamine (BT851).Boll. Chim. Farm. 122 (1983) 27–44
Thornber, E. J., Dunlop, R. H., Gawthorne, J. M. and Huxtable, C. R. Induced thiamin deficiency in lambs.Aust. Vet. J. 57 (1981) 21–26
Weber, W. and Kewitz, H. Determination of thiamine in human plasma and its pharmacokinetics.Eur. J. Clin. Pharmacol. 28 (1985) 213–219
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Rindi, G., Casirola, D., Poggi, V. et al. Thiamine transport by erythrocytes and ghosts in thiamine-responsive megaloblastic anaemia. J Inherit Metab Dis 15, 231–242 (1992). https://doi.org/10.1007/BF01799637
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DOI: https://doi.org/10.1007/BF01799637