Modifiers of ovarian function in girls and women with classic galactosemia.

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.