PDF(Sci-hub)
Abstract：
The generalized form of UDP-galactose-4\'-epimerase (GALE) deficiency causes hypotonia, failure to thrive, cataracts, and liver failure. Individuals with non-generalized forms may remain asymptomatic with uncertain long-term outcomes. We report a 2-year-old child compound heterozygous for GALE p.R51W/p.G237D who never developed symptoms of classic galactosemia but has a history of congenital combined mitral and tricuspid valve malformation and pyloric stenosis, and presented with pancytopenia. Variant pathogenicity was supported by predictive computational tools and decreased GALE activity measured in erythrocytes. GALE function extends to the biosynthesis of glycans by epimerization of UDP-N-acetyl-galactosamine and -glucosamine. Interrogation of the Gene Ontology consortium database revealed several putative proteins involved in normal hematopoiesis and atrioventricular valve morphogenesis, requiring N-glycosylation for adequate functionality. We hypothesize that by limiting substrate supply due to GALE deficiency, alterations in N-linked protein glycosylation can explain the patient\'s phenotype.
摘要：
UDP-半乳糖-4'-差向异构酶（GALE）缺乏的广义形式导致张力减退，未能茁壮成长，白内障,和肝功能衰竭。非广泛性形式的个体可能保持无症状，长期结果不确定。我们报告了GALEp.R51W/p的2岁儿童复合杂合。G237D，从未出现经典半乳糖血症的症状，但有先天性二尖瓣和三尖瓣畸形和幽门狭窄的病史，并出现全血细胞减少症.预测计算工具和红细胞中测量的降低的GALE活性支持变异的致病性。GALE功能通过UDP-N-乙酰基-半乳糖胺和-葡糖胺的差向异构化延伸到聚糖的生物合成。对基因本体论联盟数据库的询问显示了几种与正常造血和房室瓣形态发生有关的推定蛋白质，需要N-糖基化以获得足够的功能性。我们假设通过限制由于GALE缺乏而导致的底物供应，N-连接蛋白糖基化的改变可以解释患者的表型。
