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Author Notes:

Address all correspondence and requests for reprints to: Judith L. Fridovich-Keil, PhD, Department of Human Genetics, Emory University School of Medicine, Room 325.2 Whitehead Building 615 Michael Street, Atlanta, Georgia 30322. E-mail: jfridov@emory.edu.

We are grateful to the many volunteers and their families who made this work possible and to the members and leadership of the Galactosemia Foundation for all of their help with recruiting and logistics and for providing space for our study rooms at their 2010 and 2012 conferences. We also thank Luba Bensman for her skilled ultrasonography and Adrian Davis, Jason Velick, Jared Mazzola, and Philips Healthcare for providing the ultrasound machines in both Minnesota and Texas. We thank both the Massachusetts General Hospital Reproductive Endocrine Reference Lab and the Yerkes Biomarkers Core for performing AMH and FSH analyses and the Emory Genetics Lab for their assistance with recruitment.

Disclosure Summary: The authors have nothing to disclose.

Subjects:

Research Funding:

Partial funding for this work was provided by the National Institutes of Health (NIH) Grant R01 DK059904 (to J.L.F.-K.). E.L.R. was funded at different times by each of the following NIH Training Grants: T32 MH087977, TL1 RR025010, and T32 GM008367. J.R.B. was funded by NIH Training Grant T32 DK007298-31.

Modifiers of Ovarian Function in Girls and Women With Classic Galactosemia

Tools:

Journal Title:

Journal of Clinical Endocrinology and Metabolism

Volume:

Volume 98, Number 7

Publisher:

, Pages E1257-E1265

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Context: Classic galactosemia is a potentially lethal genetic disorder resulting from profound impairment of galactose-1P uridylyltransferase (GALT). More than 80% of girls and women with classic galactosemia experience primary or premature ovarian insufficiency despite neonatal diagnosis and rigorous lifelong dietary galactose restriction. Objective: The goal of this study was to test the relationship between markers of ovarian reserve, cryptic residual GALT activity, and spontaneous pubertal development in girls with classic galactosemia. Design and Setting: This was a cross-sectional study with some longitudinal follow-up in a university research environment. Patients: Patients included girls and women with classic galactosemia and unaffected controls, <1 month to 30 years old. Main Outcome Measures: We evaluated plasma anti-Müllerian hormone (AMH) and FSH levels, antral follicle counts ascertained by ultrasound, and ovarian function as indicated by spontaneous vs assisted menarche. Results: More than 73% of the pre- and postpubertal girls and women with classic galactosemia in this study, ages >3 months to 30 years, demonstrated AMH levels below the 95% confidence interval for AMH among controls of the same age, and both pre- and postpubertal girls and women with classic galactosemia also demonstrated abnormally low antral follicle counts relative to age-matched controls. Predicted residual GALT activity ≥0.4% significantly increased the likelihood that a girl with classic galactosemia would demonstrate an AMH level ≥0.1 ng/mL. Conclusions: A majority of girls with classic galactosemia demonstrate evidence of diminished ovarian reserve by 3 months of age, and predicted cryptic residual GALT activity is a modifier of ovarian function in galactosemic girls and women.

Copyright information:

© 2013 by The Endocrine Society

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