title: Modifiers of ovarian function in girls and women with classic galactosemia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This was a cross-sectional study with some longitudinal follow-up in a university research environment.
  
  
  METHODS
  Patients included girls and women with classic galactosemia and unaffected controls, <1 month to 30 years old.
  
  
  METHODS
  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.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Spencer
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Badik
authors.forename: Emily L
authors.initials: EL
authors.lastname: Ryan
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Gleason
authors.forename: K Alaine
authors.initials: KA
authors.lastname: Broadaway
authors.forename: Michael P
authors.initials: MP
authors.lastname: Epstein
authors.forename: Judith L
authors.initials: JL
authors.lastname: Fridovich-Keil
mesh_terms: D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D005693:Galactosemias / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D050505:Mutant Proteins / Q000378:metabolism; D010053:Ovary / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016649:Primary Ovarian Insufficiency / Q000000981:diagnostic imaging / Q000209:etiology*; D011627:Puberty; D011994:Recombinant Proteins / Q000378:metabolism; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics / Q000378:metabolism*; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D015415:Biomarkers; D050505:Mutant Proteins; D011994:Recombinant Proteins; D054304:Anti-Mullerian Hormone; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase