Insights into the Pathophysiology of Infertility in Females with Classical Galactosaemia

Abstract

Classical galactosaemia (CG) (OMIM 230400) is a rare inborn error of galactose metabolism caused by the deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT, EC 2.7.7.12). Primary ovarian insufficiency (POI) is the most common long-term complication experienced by females with CG, presenting with hypergonadotrophic hypoestrogenic infertility affecting at least 80% of females despite new-born screening and lifelong galactose dietary restriction. In this review, we describe the hypothesized pathophysiology of POI from CG, implications of timing of the ovarian dysfunction, and the new horizons and future prospects for treatments and fertility preservation.

Keywords: classical galactosaemia; fertility preservation; pathophysiology; primary ovarian insufficiency.

Figure 1

(a) Illustration of the pathways of galactose metabolism, with inhibition of the key enzyme: galactose-1-phosphate uridylytransferase. The key enzymes involved are shaded. (b) Illustration of the steps in oogenesis and folliculogenesis over the prenatal to menopause time period that may be influenced by GALT deficiency [16,17,18,19,20] with the proposed site of the PI3K/AKT regulation as cited by Sanchez and Smitz [20]. The abbreviations used are listed in the abbreviations list.