Heterozygosity for the Classical Galactosemia Mutation Does Not Affect Ovarian Reserve and Menopausal Age

Abstract

Female patients with classical galactosemia (galactose-1-phosphate uridyltransferase [GALT] deficiency) frequently suffer from premature ovarian failure, despite treatment with a galactose-restricted diet. Earlier research has suggested an association between heterozygosity for GALT mutations and early menopause. This study evaluates the effect of carriership for classical galactosemia on ovarian reserve and menopausal age. Proven female carriers of classical galactosemia were recruited via the Dutch Galactosemia Society. All 58 participants underwent a structured interview regarding fertility, smoking status, and menopause. To determine ovarian reserve, 42 premenopausal GALT carriers underwent ovarian antral follicle count (AFC) by transvaginal ultrasound and early follicular phase blood sampling for hormonal measurement of follicle-stimulating hormone (FSH), inhibin B, and anti-Müllerian hormone (AMH). These ovarian reserve parameters were compared with a cohort of proven fertile women (n = 166). The mean age at menopause in GALT carriers was 49.7 years, which is not different from the mean age at menopause in the general population in the Netherlands. There was no difference in FSH, inhibin B, and AMH levels or in the AFC (when corrected for age and smoking status) between 42 premenopausal GALT carriers and controls. The authors conclude that there is no evidence that GALT mutation carriership affects ovarian reserve or menopausal age.

Keywords

Galactosemia menopause anti-Müllerian hormone ovarian reserve.

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References

Suzuki M. , West C. , Beutler E. Large-scale molecular screening for galactosemia alleles in a pan-ethnic population . Hum Genet. 2001;109:210-215.

Leslie ND , Immerman EB , Flach JE , et al. The human galactose-1-phosphate uridyltransferase gene. Genomics. 1992; 14:474-480.

Holton JB , Walter JH , Tyfield LA Galactosemia. In: The Metabolic Basis of Inherited Disease . New York, NY: McGraw Hill ; 2001:1553-1583.

Schweitzer S. , Shin Y. , Jakobs C. , Brodehl J. Long-term outcome in 134 patients with galactosaemia . Eur J Pediatr. 1993; 152:36-43.

Waggoner DD , Buist NR , Donnell GN Long-term prognosis in galactosaemia: results of a survey of 350 cases . J Inherit Metab Dis. 1990;13:802-818.

Forges T. , Monnier-Barbarino P. , Leheup B. , Jouvet P. Pathophysiology of impaired ovarian function in galactosaemia. Hum Reprod Update. 2006;12:573-584.

Cramer DW , Harlow BL , Barbieri RL , Ng WG Galactose-1-phosphate uridyl transferase activity associated with age at menopause and reproductive history. Fertil Steril. 1989 ;51: 609-615.

Kaufman FR , Devgan S. , Donnell GN Results of a survey of carrier women for the galactosemia gene. Fertil Steril. 1993;60:727-728.

Sayle AE , Cooper GS , Savitz DA Menstrual and reproductive history of mothers of galactosemic children . Fertil Steril. 1996;65:534-538.

10.

Scheffer GJ , Broekmans FJM , Dorland M. , et al. Antral follicle counts by transvaginal ultrasonography are related to age in women with proven natural fertility . Fertil Steril. 1999;72:845-851.

11.

de Vet A. , Laven JS , de Jong FH , Themmen AP , Fauser BC Antimullerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril. 2002;77:357-362.

12.

Broekmans FJ , Knauff EA , te Velde ER , Macklon NS , Fauser BC Female reproductive ageing: current knowledge and future trends. Trends Endocrinol Metab. 2007;18:58-65.

13.

van Heusden AM , Fauser BCJM. Activity of the pituitary-ovarian axis in the pill-free interval during use of low-dose combined oral contraceptives . Contraception. 1999;59:237-243.

14.

Al-Qahtani A. , Muttukrishna S. , Appasamy M. , et al. Development of a sensitive enzyme immunoassay for anti-Müllerian hormone and the evaluation of potential clinical applications in males and females. Clin Endocrinol. 2005;63: 267-273.

15.

Pache TD , Wladimiroff JW , de Jong FH , Hop WC , Fauser BC Growth patterns of nondominant ovarian follicles during the normal menstrual cycle. Fertil Steril. 1990;54:638-642.

16.

Fraser IS , Shearman RP , Wilcken B. , Brown A. , Davis K. Failure to identify heterozygotes for galactosaemia in women with premature ovarian failure. Lancet. 1987;2:566.

17.

Kumar KA , Rao KL , Vedula SV , et al. Screening of the galactose-1-phosphate uridyltransferase gene in Indian women with ovarian failure. Reprod Biomed Online . 2005;11:444-448.

18.

Lukac Bajalo J , Mencej S. , Karas N. , et al. Q188R, K285N, and N314D mutation-associated alleles in the galactose-1-phosphate uridyltransferase gene and female infertility . Fertil Steril. 2005;83:776-778.

19.

Mlinar B. , Gersak K. , Karas N. , et al. Galactose-1-phosphate uridyl transferase gene mutations in women with premature ovarian failure. Fertil Steril. 2005;84:253-255.

20.

van Noord PAH , Dubas JS , Dorland M. , Boersma H. , te Velde E. Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors. Fertil Steril. 1997 ;68:95-102.

21.

McKinlay SM , Brambilla DJ , Posner JG The normal menopause transition. Maturitas. 1992;14:103-115.

22.

Hehenkamp WJ , Looman CW , Themmen AP , et al. AntiMullerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J Clin Endocrinol Metab. 2006 ;91:4057-4063.

23.

La Marca A. , Stabile G. , Artenisio AC , Volpe A. Serum antiMullerian hormone throughout the human menstrual cycle. Hum Reprod. 2006;21:3103-3107.

24.

Bosch AM , Ijlst L. , Oostheim W. , et al. Identification of novel mutations in classical galactosemia . Hum Mutat. 2005;25:502.

25.

Bandyopadhyay S. , Chakrabarti J. , Banerjee S. , et al. Prenatal exposure to high galactose adversely affects initial gonadal pool of germ cells in rats. Hum Reprod. 2003;18:276-282.

26.

Meyer WR , Doyle MB , Grifo JA , et al. Aldose reductase inhibition prevents galactose-induced ovarian dysfunction in the Sprague-Dawley rat. Am J Obstet Gynecol. 1992;167:1837-1843.

27.

Xu YK , Ng WG , Kaufman FR , Lobo RA , Donnell GN Galactose metabolism in human ovarian tissue. Pediatr Res. 1989;25:151-155.

28.

Menezo YJ , Lescaille M. , Nicollet B. , Servy EJ Pregnancy and delivery after stimulation with rFSH of a galatosemia patient suffering hypergonadotropic hypogonadism: case report. J Assist Reprod Genet. 2004;21:89-90.

29.

Prestoz LL , Couto AS , Shin YS , Petry KG Altered follicle stimulating hormone isoforms in female galactosaemia patients . Eur J Pediatr. 1997;156:116-120.

30.

Jakobs C. , Schweitzer S. , Dorland B. Galactitol in galactosemia. Eur J Pediatr. 1995;154:S50-S52.

31.

Berry GT , Nissim I. , Lin Z. , et al. Endogenous synthesis of galactose in normal men and patients with hereditary galactosaemia. Lancet. 1995 ;346:1073-1074.