Abstract
Gonadal function was followed in 26 females and 12 males with galactosaemia due to deficiency of the enzyme galactose-1-phosphate (Gal-1-P) uridyl transferase over a 4 year period. Gonadal function was normal in males, but all females except two had evidence of acquired ovarian failure. Twelve females with ovarian failure documented at the beginning of this study continued to have either primary or secondary amenorrhoea on follow-up. Five of six patients, who previously had normal gonadal function developed either hypergonadotrophic hypogonadism or an abnormal response to gonadotrophin-releasing hormone (LRH) indicative of acquired ovarian damage. Seven of eight female patients, 1–12 years of age, who were evaluated for the first time had an exaggerated release of gonadotrophins during LRH stimulation tests diagnostic of gonadal insufficiency. The pathogenesis of ovarian failure remains unknown, but it appears likely that galactose or Gal-1-P is toxic to the ovary. The source of galactose metabolites, which may begin to accumulate prenatally and continue to damage the gonad in the postnatal period, is likely to be derived from the diet and from the endogenous synthesis of Gal-1-P from glucose via a variety of metabolic pathways. The testis appears to be relatively resistant to the effects of abnormal galactose metabolism.
Similar content being viewed by others
References
Allen, J. T., Gillett, M., Holton, J. B., King, G. S. and Pettit, B. R. Evidence of galactosaemia in utero.Lancet 1 (1980) 603
Chen, Y. T., Mattison, D. R., Bercu, B. B. and Schulman, J. D. Resistance of the male gonad to a high galactose diet.Pediatr. Res. 16 (1982) 269A
Chen, Y. T., Mattison, D. R., Feigenbaum, L., Fukui, H. and Schulman, J. D. Reduction in oocyte number following prenatal exposure to a diet high in galactose.Science 214 (1981) 1145–1147
Coulam, C. B. Hormonal status of galactosaemia homozygotes.Lancet 1 (1981) 165
Donnell, G. N., Koch, R. and Bergren, W. R. Observations on results of management of galactosaemia patients. In Hsia, D. Y. (ed.)Galactosaemia, Charles C. Thomas, Springfield, IL, 1969, pp. 247–268
Gitzelmann, R. Estimation of galactose-1-phosphate in erythrocytes: a rapid and simple enzymatic method.Clin. Chim. Acta 26 (1969) 313–316
Gitzelmann, R., Hansen, R. G. and Steinmann, B. Biogenesis of galactose, a possible mechanism of self-intoxication in galactosaemia. In Hommes, F. A. and Van den Bergh, C. J. (eds.)Normal and Pathological Development of Energy Metabolism, Academic Press, London, 1975, pp. 25–37
Goebelsmann, U., Bernstein, G. S., Gale, J. A., Kletzky, O. A., Nakamura, R. M., Coulson, A. H. and Korelitz, J. J. Serum gonadotrophin, testosterone, estradiol and estrone levels prior to and following bilateral vasectomy. In Lepow, I. H. and Crozier, R. (eds.)Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, Academic Press, New York, 1978, pp. 165–181
Grumbach, M. M., Roth, J. C., Kaplan, S. L. and Kelch, R. P. Hypothalamic-pituitary regulation of puberty in man: evidence and concepts derived from clinical research. In Grumbach, M. M., Grave, G. D. and Mayer, F. E. (eds.)Control of the Onset of Puberty, John Wiley, New York, 1974, pp. 115–166
Hoefnagel, D., Wurster-Hili, D. and Child, E. L. Ovarian failure in galactosaemia.Lancet 2 (1979) 1197
Kaufman, F. R., Kogut, M. D., Donnell, G. N., Goebelsmann, U., March C. and Koch, R. Hypergonadotrophic hypogonadism in female patients with galactosaemia.N. Engl. J. Med. 304 (1981) 994–998
Komrower, G. M. Ovarian failure in galactosaemia.Lancet 2 (1979) 1021
Komrower, G. M. Clouds over galactosaemia.Lancet 1 (1983) 190
Levy, H. L., Driscoll, S. G., Porensky, R. S. and Wender, D. F. Ovarian failure in galactosaemia.N. Engl. J. Med. 310 (1984) 50
Midgley, A. R. Jr. Radioimmunoassay: a method for human chorionic gonadotrophin and human luteinizing hormone.Endocrinology 79 (1966) 10–18
Midgley, A. R. Jr. Radioimmunoassay for human follicle-stimulating hormone.J. Clin. Endocrinol. Metab. 27 (1967) 295–299
Nakamura, R. M., Nagata, Y., Osborn, C. and Mishell, D. R. Jr. Use of postmenopausal serum pool as a reference preparation for RIA of gonadotrophins.Acta. Endocrinol. 75 (1974) 478–490
Siler, T. M. and Yen, S. S. C. Augmented gonadotrophin response to synthetic LRF in hypogonadal state.J. Clin. Endocrinol. Metab. 37 (1973) 491–494
Steinmann, B., Gitzelmann, R. and Zachmann, M. Hypogonadism and galactosaemia.N. Engl. J. Med. 305 (1981) 464
Tanner, J.Growth at Adolescence, 2nd Edn., Charles C. Thomas, Springfield, IL, 1962, pp. 32–33
Vannas, A., Hogan, M. J. and Golbus, M. S. Lens changes in a galactosaemic fetus.Am. J. Ophthalmol. 80 (1975) 726
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kaufman, F.R., Donnell, G.N., Roe, T.F. et al. Gonadal function in patients with galactosaemia. J Inherit Metab Dis 9, 140–146 (1986). https://doi.org/10.1007/BF01799450
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01799450