Risk factors for premature ovarian failure in females with galactosemia.
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.


METHODS
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).


CONCLUSIONS
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.
Guerrero
N V
NV
Division of Medical Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Singh
R H
RH
Manatunga
A
A
Berry
G T
GT
Steiner
R D
RD
Elsas
L J
LJ
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005693:Galactosemias / Q000150:complications* / Q000178:diet therapy / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D017354:Point Mutation / Q000235:genetics; D016649:Primary Ovarian Insufficiency / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000097:blood / Q000235:genetics
D005640:Follicle Stimulating Hormone; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase