Division of Metabolic Diseases, Department of Paediatrics, University Hospital of Padua, Padua, Italy.
Cardiomyology and Medical Genetics, Department of Experimental Medicine, Second University of Naples, Naples, Italy.
Clin Genet. 2018 Feb;93(2):206-215. doi: 10.1111/cge.13030. Epub 2017 Aug 9.
Galactosemia type 1 is an autosomal recessive disorder of galactose metabolism, determined by a deficiency in the enzyme galactose-1-phosphate uridyltransferase (GALT). GALT deficiency is classified as severe or variant depending on biochemical phenotype, genotype and potential to develop acute and long-term complications. Neonatal symptoms usually resolve after galactose-restricted diet; however, some patients, despite the diet, can develop long-term complications, in particular when the GALT enzyme activity results absent or severely decreased. The mechanisms of acute and long-term complications are still discussed and several hypotheses are presented in the literature like enzymatic inhibition, osmotic stress, endoplasmic reticulum stress, oxidative stress, defects of glycosylation or epigenetic modification. This review summarizes the current knowledge of galactosemia, in particular the putative mechanisms of neonatal and long-term complications and the molecular genetics of GALT deficiency.
半乳糖血症 1 型是一种常染色体隐性遗传的半乳糖代谢紊乱，由半乳糖-1-磷酸尿苷酰转移酶（GALT）缺乏引起。根据生化表型、基因型和发展急性和长期并发症的潜力，GALT 缺乏症分为严重型或变异型。在限制半乳糖饮食后，新生儿症状通常会得到缓解；然而，尽管进行了饮食控制，一些患者仍可能出现长期并发症，尤其是当 GALT 酶活性完全缺失或严重降低时。急性和长期并发症的机制仍在讨论中，文献中提出了几种假说，如酶抑制、渗透应激、内质网应激、氧化应激、糖基化缺陷或表观遗传修饰。本综述总结了半乳糖血症的最新知识，特别是新生儿和长期并发症的可能机制以及 GALT 缺乏症的分子遗传学。
