Vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT).

To follow-up our previous observation that vaginal agenesis might be associated with decreased activity of galactose-1-phosphate uridyl transferase (GALT), we studied activity and genotype of GALT in 13 daughters with vaginal agenesis and their mothers. For comparison, GALT measurements were available from 113 pre-menopausal women with no known Müllerian anomalies selected from the general population. Red cell GALT activity was significantly lower in both the daughters and their mothers in comparison with general population controls. Six out of thirteen (46%) daughters and two mothers of the remaining seven daughters (29%) were carriers for the N314D mutation of GALT associated with the Duarte variant of galactosaemia as compared to 16 out of 113 general population controls (14%) who possessed at least one N314D allele. Pigmentary skin changes and scoliosis were associated phenotypic findings in daughters with vaginal agenesis. We conclude that fetal or maternal GALT mutations that decrease GALT activity may be associated with vaginal agenesis and have, as their possible biological basis, increased intrauterine exposure to galactose which has been demonstrated in rodents to cause decreased oocyte survival and delayed vaginal opening in offspring.