ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Assist Reprod Genet. 2018 Jul; 35(7):1209.

Galactosemia is an autosomal recessive genetic disorder of the galactose metabolism, caused by impaired activity of galactose-1-phosphate uridyltransferase (GALT). Complete deficiency or severely reduced activity of GALT affects approximately 1:30,000 to 1:50,000 persons. Girls and women with classic galactosemia have reduced ovarian reserve with elevated serum levels of follicle-stimulating hormone (FSH) and reduced concentrations of anti-Müllerian hormone (AMH) compared to age-matched controls (1–2). It has been estimated that more than 80% of girls with classic galactosemia experience premature ovarian insufficiency in early adulthood. The pathogenesis of the observed accelerated follicle loss is unknown.

In this retrospective study, follicle density was estimated in ovarian cortical tissues from six pre-pubertal girls with galactosemia below the age of 12 years, and from 31 girls below the age of 18 years who had one ovary removed for fertility preservation prior to gonadotoxic treatment. Expression of AMH and other glycoproteins important for follicle development was analyzed with immunohistochemistry. Girls with galactosemia below the age of 5 years presented with morphological normal follicles and follicle densities within the 95% confidence interval of controls. No follicles were detected in the ovary from an 11.7-year-old girl with galactosemia. The expression of specific glycoproteins was not significantly different in girls with galactosemia and in controls.

These findings suggest that young girls with galactosemia maintain vital follicles during the first years of life, and cryopreservation of ovarian tissue in early childhood may represent a therapeutic option for future fertility in this patient group.

References: 1. Sanders RD, Spencer JB, Epstein MP, Pollak SV, Vardhana PA, Lustbader JW, Fridovich-Keil JL. Biomarkers of ovarian function in girls and women with classic galactosemia. Fertil Steril. 2009; 92: 344–351.

2. Spencer JB, Badik JR, Ryan EL, Gleason TJ, Broadaway KA, Epstein MP, Fridovich-Keil JL. Modifiers of ovarian function in girls and women with classic galactosemia. J Clin Endocrinol Metab. 2013; 98: E1257–1265.