Presentation, progression, and predictors of ovarian insufficiency in classic galactosemia

Abstract

Classic galactosemia (CG) is an inherited metabolic disorder that affects about 1 in 50,000 live births in the United States and many other countries. With the benefit of early detection by newborn screening and rapid dietary restriction of galactose, generally achieved by removing dairy from the diet, most affected infants are spared the acute and potentially lethal symptoms of disease. Despite early detection and life-long dietary intervention, however, most patients grow to experience a constellation of long-term complications that include premature ovarian insufficiency in the vast majority of girls and young women. Our goal in the study reported here was to define the presentation, progression, and predictors of ovarian insufficiency in a cohort of 102 post-pubertal girls and women with CG. To our knowledge, this is the largest cohort studied to date. We found that 68% of the girls and women in our study achieved spontaneous menarche, while 32% achieved menarche only after starting hormone replacement therapy (HRT). Of those who achieved spontaneous menarche, fewer than 50% were still cycling regularly after 3 years, and fewer than 15% were still cycling regularly after 10 years. Of factors tested for possible association with spontaneous menarche, only detectable (≥ 0.04 ng/mL) plasma anti-Müllerian hormone (AMH) level was significant. These results extend substantially from prior studies and confirm that detectable plasma AMH is a useful predictor of ovarian function in girls and women with CG.