Risk factors for premature ovarian failure in females with galactosemia

J Pediatr. 2000 Dec;137(6):833-41. doi: 10.1067/mpd.2000.109148.

Abstract

The risk for premature ovarian failure (POF) in females with galactosemia can be predicted by analyzing 3 areas of risk pathology: the patient's molecular genotype for galactose-1-phosphate uridyltransferase (GALT), alternate pathways for galactose metabolism, and the patient's environment at diagnosis and during treatment.

Study design: Retrospective cross-sectional information was collected on 53 females with classic galactosemia, and their ovarian function was analyzed by determination of serum follicle-stimulating hormone and luteinizing hormone levels and by clinical observation. The associations were analyzed between POF and the mutations in GALT, the highest erythrocyte galactose-1-phosphate (Gal-1-P) level at diagnosis, the age at which dietary treatment was initiated, mean erythrocyte Gal-1-P level during treatment, and whole-body carbon 13-labeled galactose oxidation to (13)CO(2).

Results: The most prevalent mutation, Q188R, had a significant effect of genotype category (Q188R/Q188R, Q188R/Other, Other/Other) on POF (P =.04, Fisher exact test and an odds ratio of 8.3). Mean erythrocyte Gal-1-P level during treatment was a significant risk factor for POF (P =.04). Also, all patients studied with less than 5% total body oxidation of galactose to (13)CO(2) had POF, whereas those with more than 5% did not have POF (P =.008, Fisher exact test).

Conclusion: The development of POF in females with galactosemia is more likely if the patient's genotype is Q188R/Q188R, if the mean erythrocyte Gal-1-P is >3.5 mg/dL during therapy, and if the recovery of (13)CO(2) from whole-body (13)C-galactose oxidation is reduced below 5% of administered (13)C-galactose.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Female
  • Follicle Stimulating Hormone / blood
  • Galactosemias / complications*
  • Galactosemias / diet therapy
  • Galactosemias / genetics
  • Genotype
  • Humans
  • Infant
  • Point Mutation / genetics
  • Primary Ovarian Insufficiency / diagnosis
  • Primary Ovarian Insufficiency / epidemiology
  • Primary Ovarian Insufficiency / etiology*
  • Retrospective Studies
  • Risk Factors
  • UTP-Hexose-1-Phosphate Uridylyltransferase / blood
  • UTP-Hexose-1-Phosphate Uridylyltransferase / genetics

Substances

  • Follicle Stimulating Hormone
  • UTP-Hexose-1-Phosphate Uridylyltransferase