Endometriosis associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT)

To explore a possible connection between endometriosis, Müllerian anomalies, and possession of the N314D allele of the gene for galactose-1-phosphate uridyl transferase (GALT), we studied 33 women with endometriosis attending a fertility clinic. Patients completed questionnaires and had DNA tested for the N314D mutation of GALT. A previously completed general population survey of 111 women which obtained the same information was available for comparison. Women with endometriosis were more likely to carry at least one N314D allele (30% compared with 14%) and more likely to report a medical history of scoliosis (21% compared with 2%) compared to general population controls: two features we have described in women with vaginal agenesis. Compared with endometriosis cases without the N314D allele, those cases with the allele tended to have more advanced disease and a family history of endometriosis. We speculate that endometriosis may arise due to defects of canalization of the cervix leading to cervical stenosis and retrograde menstruation. The relevance of the N314D mutation, via this model, may derive from an association between abnormalities of galactose metabolism and vaginal agenesis which represents a canalization defect of the vaginal plate of the Müllerian tubercle, the same structure which gives rise to the cervix.