Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Pediatrics, Department of Clinical Genetics, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Metabolism. 2018 Jun;83:188-196. doi: 10.1016/j.metabol.2018.01.025. Epub 2018 Jan 31.
Hereditary galactosemia is an inborn error of carbohydrate metabolism. Galactose is metabolized by Leloir pathway enzymes; galactokinase (GALK), galactose-1-phosphate uridylyltransferase (GALT) and UDP-galactose 4-epimerase (GALE). The defects in these enzymes cause galactosemia in an autosomal recessive manner. The severe GALT deficiency, or classic galactosemia, is life-threatening in the newborn period. The treatment for classic galactosemia is dietary restriction of lactose. Although implementation of lactose restricted diet is efficient in resolving the acute complications, it is not sufficient to prevent long-term complications affecting the brain and female gonads, the two main target organs of damage. Implementation of molecular genetics diagnostic tools and GALT enzyme assays are instrumental in distinguishing classic galactosemia from clinical and biochemical variant forms of GALT deficiency. Better understanding of mechanisms responsible for the phenotypic variation even within the same genotype is essential to provide appropriate counseling for families. Utilization of a lactose restricted diet is also recommended for GALK deficiency and some rare forms of GALE deficiency. Novel modes of therapies are being explored; they may be beneficial if access issues to the affected tissues are circumvented and optimum use of therapeutic window is achieved.
遗传性半乳糖血症是一种先天性碳水化合物代谢紊乱。半乳糖由 Leloir 途径的酶代谢；半乳糖激酶（GALK）、半乳糖-1-磷酸尿苷酰转移酶（GALT）和 UDP-半乳糖 4-差向异构酶（GALE）。这些酶的缺陷以常染色体隐性方式导致半乳糖血症。严重的 GALT 缺乏症，或经典半乳糖血症，在新生儿期具有生命威胁。经典半乳糖血症的治疗方法是限制乳糖饮食。尽管实施乳糖限制饮食在解决急性并发症方面非常有效，但不足以预防影响大脑和女性性腺的长期并发症，这是两个主要的靶器官损伤。分子遗传学诊断工具和 GALT 酶测定的实施有助于将经典半乳糖血症与 GALT 缺乏症的临床和生化变异形式区分开来。更好地了解导致表型变异的机制，即使在相同的基因型内，对于为家庭提供适当的咨询至关重要。对于 GALK 缺乏症和一些罕见形式的 GALE 缺乏症，也建议使用乳糖限制饮食。正在探索新的治疗模式；如果能够避免对受影响组织的访问问题并实现治疗窗口的最佳利用，它们可能会有益。
