Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Apr;79(4):1039–1043. doi: 10.1172/JCI112916

Transketolase abnormality in cultured fibroblasts from familial chronic alcoholic men and their male offspring.

A B Mukherjee, S Svoronos, A Ghazanfari, P R Martin, A Fisher, B Roecklein, D Rodbard, R Staton, D Behar, C J Berg, et al.
PMCID: PMC424281  PMID: 3558815

Abstract

We have investigated a thiamine-dependent enzyme, transketolase, in cultured fibroblasts from 41 human subjects, including patients with alcoholism-associated Wernicke-Korsakoff syndrome (n = 3), familial chronic alcoholic males (n = 7), their sons (n = 7), nonalcoholic men (n = 7), their male offspring (n = 7), and three generations of an Amish family (n = 10) without any history of alcoholism. This study was undertaken to delineate whether transketolase abnormality (i.e., high Michaelis Menton constant (Km) for thiamine pyrophosphate), previously reported in patients with Wernicke-Korsakoff syndrome is prevalent among familial chronic alcoholic men and their sons without prior history of alcohol abuse but who are at high risk for alcoholism. Our data suggest that an inborn error (i.e., high Km of transketolase for thiamine pyrophosphate) predisposing to thiamine deficiency diseases similar to those reported in Wernicke-Korsakoff syndrome may occur in the general population. However, for some as yet unexplained reason(s) this variant seems to occur more frequently among familial chronic alcoholic men and their male offspring without any history of alcoholism. The inheritance pattern of this enzyme variant as revealed from an Amish pedigree study may be autosomal recessive as previously suggested.

Full text

PDF
1039

Images in this article

1042Image
on p.1042

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Behar D., Berg C. J., Rapoport J. L., Nelson W., Linnoila M., Cohen M., Bozevich C., Marshall T. Behavioral and physiological effects of ethanol in high-risk and control children: a pilot study. Alcohol Clin Exp Res. 1983 Fall;7(4):404–410. doi: 10.1111/j.1530-0277.1983.tb05495.x. [DOI] [PubMed] [Google Scholar]
  2. Blass J. P., Gibson G. E. Abnormality of a thiamine-requiring enzyme in patients with Wernicke-Korsakoff syndrome. N Engl J Med. 1977 Dec 22;297(25):1367–1370. doi: 10.1056/NEJM197712222972503. [DOI] [PubMed] [Google Scholar]
  3. Blass J. P., Gibson G. E. Genetic factors in Wernicke-Korsakoff syndrome. Alcohol Clin Exp Res. 1979 Apr;3(2):126–134. doi: 10.1111/j.1530-0277.1979.tb05286.x. [DOI] [PubMed] [Google Scholar]
  4. Childs B. Sir Archibald Garrod's conception of chemical individuality: a modern appreciation. N Engl J Med. 1970 Jan 8;282(2):71–77. doi: 10.1056/NEJM197001082820205. [DOI] [PubMed] [Google Scholar]
  5. DREYFUS P. M. The quantitative histochemical distribution of thiamine in deficient rat brain. J Neurochem. 1961 Nov;8:139–145. doi: 10.1111/j.1471-4159.1961.tb13535.x. [DOI] [PubMed] [Google Scholar]
  6. Feighner J. P., Robins E., Guze S. B., Woodruff R. A., Jr, Winokur G., Munoz R. Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry. 1972 Jan;26(1):57–63. doi: 10.1001/archpsyc.1972.01750190059011. [DOI] [PubMed] [Google Scholar]
  7. HSU J. M., CHOW B. F. Effect of thiamine deficiency on glutathione contents of erythrocytes and tissues in the rat. Proc Soc Exp Biol Med. 1960 Jun;104:178–180. doi: 10.3181/00379727-104-25771. [DOI] [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. McCandless D. W., Schenker S., Cook M. Encephalopathy of thiamine deficieny: studies of intracerebral mechanisms. J Clin Invest. 1968 Oct;47(10):2268–2280. doi: 10.1172/JCI105912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mendelson J. H., Mello N. K. Medical progress. Biologic concomitants of alcoholism. N Engl J Med. 1979 Oct 25;301(17):912–921. doi: 10.1056/NEJM197910253011704. [DOI] [PubMed] [Google Scholar]
  11. Mukherjee A. B., Ghazanfari A., Svoronos S., Staton R. C., Nakada T., Kwee I. L. Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy. Neurology. 1986 Nov;36(11):1508–1510. doi: 10.1212/wnl.36.11.1508. [DOI] [PubMed] [Google Scholar]
  12. Nadi N. S., Nurnberger J. I., Jr, Gershon E. S. Muscarinic cholinergic receptors on skin fibroblasts in familial affective disorder. N Engl J Med. 1984 Jul 26;311(4):225–230. doi: 10.1056/NEJM198407263110404. [DOI] [PubMed] [Google Scholar]
  13. Omenn G. S., Motulsky A. G. A biochemical and genetic approach to alcoholism. Ann N Y Acad Sci. 1972 May 25;197:16–23. doi: 10.1111/j.1749-6632.1972.tb28112.x. [DOI] [PubMed] [Google Scholar]
  14. Schuckit M. A., Goodwin D. A., Winokur G. A study of alcoholism in half siblings. Am J Psychiatry. 1972 Mar;128(9):1132–1136. doi: 10.1176/ajp.128.9.1132. [DOI] [PubMed] [Google Scholar]
  15. VICTOR M., ADAMS R. D. On the etiology of the alcoholic neurologic diseases with special reference to the role of nutrition. Am J Clin Nutr. 1961 Jul-Aug;9:379–397. doi: 10.1093/ajcn/9.4.379. [DOI] [PubMed] [Google Scholar]
  16. Weingartner H., Grafman J., Boutelle W., Kaye W., Martin P. R. Forms of memory failure. Science. 1983 Jul 22;221(4608):380–382. doi: 10.1126/science.6867715. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES