Guerrero N V, Singh R H, Manatunga A, Berry G T, Steiner R D, Elsas L J
Division of Medical Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
J Pediatr. 2000 Dec;137(6):833-41. doi: 10.1067/mpd.2000.109148.
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.
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).
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).
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.
通过分析三个风险病理领域，可以预测半乳糖血症女性发生卵巢早衰（POF）的风险：患者的1-磷酸半乳糖尿苷转移酶（GALT）分子基因型、半乳糖代谢的替代途径以及患者在诊断和治疗期间的环境。
收集了53例经典型半乳糖血症女性的回顾性横断面信息，并通过测定血清促卵泡激素和促黄体生成素水平以及临床观察来分析她们的卵巢功能。分析了POF与GALT突变、诊断时最高红细胞1-磷酸半乳糖（Gal-1-P）水平、开始饮食治疗的年龄、治疗期间平均红细胞Gal-1-P水平以及全身碳13标记半乳糖氧化为（13）CO2之间的关联。
最常见的突变Q188R对POF的基因型类别（Q188R/Q188R、Q188R/其他、其他/其他）有显著影响（P =.04，Fisher精确检验，优势比为8.3）。治疗期间平均红细胞Gal-1-P水平是POF的显著危险因素（P =.04）。此外，所有全身半乳糖氧化为（13）CO2不足5%的研究患者均发生了POF，而氧化超过5%的患者未发生POF（P =.008，Fisher精确检验）。
半乳糖血症女性如果基因型为Q188R/Q188R、治疗期间平均红细胞Gal-1-P>3.5 mg/dL以及全身（13）C-半乳糖氧化产生的（13）CO2回收率降至低于给予的（13）C-半乳糖的5%，则更有可能发生POF。
