Skip to main content
SpringerLink
Log in

Further studies on erythrocyte thiamin transport and phosphorylation in seven patients with thiamin-responsive megaloblastic anaemia

  • Published:
Journal of Inherited Metabolic Disease

Summary

Erythrocyte thiamin metabolism and transport were investigated in 7 patients from Brazil, Israel and Italy suffering from thiamin-responsive megaloblastic anaemia (TRMA) associated with diabetes mellitus and sensorineural deafness. All patients discontinued thiamin therapy for 4–7 days before the investigation. TRMA patients showed invariably reduced total thiamin levels in erythrocytes (percentage reduction compared with healthy controls, −46.8±3%; mean±SEM). The proportions of individual thiamin compounds, expressed as a percentage of total thiamin content, were within the normal range, whereas their absolute amounts were significantly decreased in the following order: thiamin monophosphate > thiamin pyrophosphate > thiamin. Thiamin pyrophosphokinase activity was also reduced as compared with controls (mean reduction±SEM, −25.9±1%). The saturable, specific component of thiamin uptake, which normally prevails at physiological concentrations of thiamin (<2µmol/L), was absent in erythrocytes obtained from TRMA patients, while the non-saturable (diffusive) component of uptake was normally present.

These results confirm observations made previously in two patients and demonstrate that TRMA is consistently associated with a state of thiamin deficiency, which is presumably secondary to reduced thiamin cellular transport and absorption (caused by lack of a membrane-specific carrier), and to impaired intracellular pyrophosphorylation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abboud MR, Alexander D, Najjar SS (1985) Diabetes mellitus, thiamine-dependent megaloblastic anemia, and sensorineural deafness associated with deficient α-ketoglutarate dehydrogenase activity.J Pediatr 107: 537–541.

    Google Scholar 

  • Bettendorff L, Grandfils C, De Rycker C, Schoffeniels E (1986) Determination of thiamine and its phosphate esters in human blood serum at femtomole levels.J Chromatogr Biomed Appl 382: 297–302.

    Google Scholar 

  • Casirola D, Ferrari G, Gastaldi G, Patrini C, Rindi G (1988) Transport of thiamine by brush border membrane vesicles from rat small intestine.J Physiol (London) 398: 329–339.

    Google Scholar 

  • Casirola D, Patrini C, Ferrari G, Rindi G (1990) Thiamine transport by human erythrocytes and ghosts.J Membrane Biol 118: 11–18.

    Google Scholar 

  • Cusaro G, Rindi G, Sciorelli G (1977) Subcellular distribution of thiamine-pyrophosphokinase and thiamine-pyrophosphatase activities in rat isolated enterocytes.Int J Vit Nutr Res 47: 99–106.

    Google Scholar 

  • De Caro LG Jr. (1962) Vitesse de conduction et contenu en thiamine (cocarboxylase) du nerf.Electroencephalogr Clin Neurophysiol 14 (supplement 22): 26–29.

    Google Scholar 

  • Deus D, Blum H (1970) Subcellular distribution of thiamine pyrophosphokinase activity in rat liver and erythrocytes.Biochim Biophys Acta 219: 489–492.

    Google Scholar 

  • Feldheim W (1966) Changes in enzyme activities induced by nutritional deficiencies. II. Determination of the state of saturation with thiamine by biochemical methods.Int J Vit Nutr Res 36: 197–200.

    Google Scholar 

  • Fennelly J, Frank O, Baker H, Leevy CM (1964) Transketolase activity in experimental thiamine deficiency and hepatic necrosis.Proc Soc Exp Biol Med 116: 875–877.

    Google Scholar 

  • Grill J, Leblanc T, Baruchel A, Daniel MT, Dresch C, Schaison G (1991) Thiamine responsive anemia: Report of a new case associated with a thiamine pyrophosphokinase deficiency.Nouv Rev Fr Hématol 33: 543–544.

    Google Scholar 

  • Gubler CJ (1969) Thiamine and heart function.J Vitaminol 15: 346–348.

    Google Scholar 

  • Hakim AM, Carpenter S, Pappius HM (1983) Metabolic and histological reversibility of thiamine deficiency.J Cerebr Blood Flow Metab 3: 468–477.

    Google Scholar 

  • Hell D, Six P, Salked R (1976) Vitamin B1-Mangel bei chronischen Äthylikern und sein klinisches Korrelat.Schweitz Med Wochenschr 106: 1466–1470.

    Google Scholar 

  • Inouye K, Katsura E (1965) Clinical signs and metabolism of beriberi patients. In Shimazono N, Katsura E, eds.Review of Japanese Literature on Beriberi and Thiamine. Tokyo: Igaku Shoin, 29–63.

    Google Scholar 

  • Kuriyama M, Mizuma A, Yokomine R, Igata A, Otuji U (1980) Erythrocyte transketolase activity in uremia.Clin Chim Acta 108: 169–177.

    Google Scholar 

  • Laforenza U, Patrini C, Gastaldi G, Rindi G (1990) Effect 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: 591–603.

    Google Scholar 

  • Lonsdale D, Nodar RH, Orlowski JP (1982) Brainstem dysfunction in infants responsive to thiamine disulfide: preliminary studies in four patients.Clin Encephalography 13: 82–88.

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent.J Biol Chem 193: 265–275.

    Google Scholar 

  • Mandel H, Berant M, Hazani A, Naveh Y (1984) Thiamine-dependent beriberi in the ‘thiamine-responsive anemia syndrome’.N Engl J Med 311: 836–838.

    Google Scholar 

  • Mandel H, Vardi P, Gershoni-Baruch, Patrini C, Berant M (1994) Thiamine responsive diabetes: a novel category of diabetes.N Engl J Med submitted.

  • McCandless DW, Schenker S (1968) Encephalopathy of thiamine deficiency: studies of intracerebral mechanisms.J Clin Invest 47: 2268–2280.

    Google Scholar 

  • Niederhoff H, Kunzer W (1969) Thiamine-beduerftige megaloblastische Anämie.Deutsch Med Wochenschr 94: 2000–2003.

    Google Scholar 

  • Poggi V, Rindi G, Patrini C, De Vizia B, Longo G, Andria G (1989) Studies on thiamine metabolism in thiamine-responsive megaloblastic anaemia.Eur J Pediatr 148: 307–311.

    Google Scholar 

  • Rathanaswami P, Sundaresan R (1988) Effects of insulin secretagogues on the secretion of insulin during thiamine deficiency.Biochem Int 17: 523–528.

    Google Scholar 

  • Rathanaswami P, Sundaresan R (1991) Effects of thiamine deficiency on the biosynthesis of insulin in rats.Biochem Int 24: 1057–1062.

    Google Scholar 

  • Ricci V, Rindi G (1992) Thiamin uptake by rat isolated enterocytes: relationship between transport and phosphorylation.Arch Int Physiol Biochim Biophys 100: 275–279.

    Google Scholar 

  • Rindi G, Ventura U (1972) Thiamine intestinal transport.Physiol Rev 52: 821–827.

    Google Scholar 

  • Rindi G, Casirola D, Poggi V, De Vizia B, Patrini C, Laforenza U (1992) Thiamine transport by erythrocytes and ghosts in thiamine-responsive megaloblastic anaemia.J Inher Metab Dis 15: 231–242.

    Google Scholar 

  • Rinehart JF, Greenberg LD, Ginzton LL (1948) Thiamine deficiency in the Rhesus monkey.Blood 3: 1453–1459.

    Google Scholar 

  • Rinehart JF, Friedman M, Greenberg LD (1949) Effect of experimental thiamine deficiency on the nervous system of the Rhesus monkey.Arch Pathol 48: 129–139.

    Google Scholar 

  • Rodger FC (1953) Experimental thiamin deficiency as a cause of degeneration in the visual pathway of the rat.Br J Ophthalmol 37: 11–29.

    Google Scholar 

  • Rogers LE, Porter FS, Sidbury JB (1969) Thiamin-responsive megaloblastic anemia.J Pediatr 74: 494–504.

    Google Scholar 

  • Rosskamp R, Zigrahn W, Burmeister W (1985) Thiaminabhängige Anämie und Trombozytopenie, insulinpflichtiger Diabetes mellitus und sensorineurale Schwerhörigkeit — Fallbeschreibung und Ubersicht.Klin Pädriatr 197: 315–317.

    Google Scholar 

  • Rossouw JE, Labadarious D, Krasner N, Davis M, Williams R (1978) Red blood cell transketolase activity and the effect of thiamine supplementation in patients with chronic liver diseases.Scand J Gastroenterol 13: 133–138.

    Google Scholar 

  • Sanioto SML, Reinauer H, Hollman S (1977) Thiamine pyrophosphokinase activity in liver, heart and brain crude extracts of control and thiamine deficient rats.Int J Vit Nutr Res 47: 315–324.

    Google Scholar 

  • Shigematsu Y, Nakai A, Kuriyama M et al (1990) Delayed auditory brainstem response in thiamin-deficient rats.J Nutr Sci Vitaminol 36: 209–215.

    Google Scholar 

  • Sutherland JB, Jaussi AW, Gubler CJ (1974) The effect of thiamine deprivation, and oxythiamine- and pyrithiamine-treatment on cardiac function and metabolism in the rat.J Nutr Sci Vitaminol 20: 35–54.

    Google Scholar 

  • Tallaksen CME, Bell H, Bøhmer T (1993) Thiamin and thiamin phosphate ester deficiency assessed by high performance liquid chromatography in four clinical cases of Wernicke encephalopathy.Alcohol Clin Exp Res 17: 712–716.

    Google Scholar 

  • Thornberg EJ, Dunlop RH, Gawthorne JM, Huxtable CR (1981) Induced thiamine deficiency in lambs.Aust Vet J 57: 21–26.

    Google Scholar 

  • Viana MB, Carvalho RI (1978) Thiamine-responsive megaloblastic anemia, sensorineural deafness, and diabetes mellitus: a new syndrome?J Pediatr 93: 235–238.

    Google Scholar 

  • Waldenlind L, Borg S, Vikander B (1981) Effect of peroral thiamine treatment on thiamine content and transketolase activity of red blood cells in alcoholic patients.Acta Med Scand 209: 209–212.

    Google Scholar 

  • Warnock LG, Prudhomme CR, Wagner C (1978) The determination of thiamine pyrophosphate in blood and other tissues, and its correlation with erythrocyte transketolase activity.J Nutr 108: 421–427.

    Google Scholar 

  • Weissberg A, Beatty GH (1960) Tables of tolerance-limit factors for normal distribution.Technometrics 2: 483–500.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Human Physiology, University of Pavia, Via Forlanini 6, I-27100, Pavia, Italy

    G. Rindi, C. Patrini & U. Laforenza

  2. Department of Pediatrics, Rambam Medical Center, Bat Galim, 31096, Haifa, Israel

    H. Mandel & M. Berant

  3. Department of Pediatrics, Faculty of Medicine at UFMG, Av. A. Balena 190, 30130-100, Belo Horizonte, Brazil

    M. B. Viana

  4. Department of Pediatrics - Haematology, Pausilipon Hospital, I-80123, Naples, Italy

    V. Poggi & A. N. F. Zarra

Authors
  1. G. Rindi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Patrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U. Laforenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Mandel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Berant
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. B. Viana
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. Poggi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. N. F. Zarra
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rindi, G., Patrini, C., Laforenza, U. et al. Further studies on erythrocyte thiamin transport and phosphorylation in seven patients with thiamin-responsive megaloblastic anaemia. J Inherit Metab Dis 17, 667–677 (1994). https://doi.org/10.1007/BF00712009

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00712009

Keywords

Search

Navigation