Gonadal function in patients with galactosaemia

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.

Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene

“…For example, in the absence of Xaa-Pro aminopeptidase, circulating Xaa-Pro-containing peptides might accumulate in oocytes and be toxic. An analogous mechanism has been proposed for POF in women with galac-tosemia, which is that the elevated galactose or galactose-1-phosphate levels interfere with oocyte function (Kaufman et al, 1986).…”

Diagnostic Quandary: Premature Ovarian Failure and Galactosemia Variants in Adolescent Girls with Delayed Puberty

“…In contrast to affected females, males typically have normal gonadotropin levels and normal testicular function, 7 suggesting the testis appears to be resistant to the effects of abnormal galactose metabolism. 8 This may be because GALT expression in the testis is lower than anywhere else in the body. 9 While ovarian failure associated with galactosemia is thought to be associated with the metabolites that accumulate due to the disease, the exact etiology of the failure is still unclear.…”

Pregnancy and Delivery After Stimulation with rFSH of a Galatosemia Patient Suffering Hypergonadotropic Hypogonadism: Case Report

“…It has been generally admitted that galactose and its metabolites could be toxic to the ovary (1)(2). This generally leads to more or less severe hypergonadotropic hypogonadism.…”