Defective GALE causes EDG

Cytosolic UDP-galactose 4'-epimerase (GALE) catalyses the reversible interconversion of UDP-D-galactose (UDP-Gal) and UDP-glucose (UDP-Glc), the third reacton in the Leloir pathway of galactose metabolism. GALE can also catalyse the epimerisation of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The active form of the enzyme is a homodimer with one molecule of bound NAD per monomer (GALE:NAD+ dimer). Defects in GALE can cause Epimerase-deficiency galactosemia (EDG; MIM:230350), or type III galactosemia (diseases of galactose metabolism) whose clinical features include early-onset cataracts, liver damage, deafness and mental retardation. Historically, it was considered that there were two forms of GALE deficidency; a benign ("peripheral") form where there is no GALE activity in red blood cells and characterised by mild symptoms (Gitzelmann 1972) and a rarer "generalised" form with no detectable GALE activity in all tissues resulting in more severe symptoms (Holton et al. 1981). The disease is now considered to be a continuum (Openo et al. 2006).

细胞质UDP-半乳糖4'-异构酶（GALE）催化UDP-D-半乳糖（UDP-Gal）和UDP-葡萄糖（UDP-Glc）之间的可逆互变反应，该反应是半乳糖代谢Leloir途径中的第三步反应。GALE还能够催化UDP-N-乙酰葡萄糖胺的异构化反应，生成UDP-N-乙酰半乳糖胺。该酶的活性形式是一种由两个分子组成同源二聚体，每个单体与一个NAD分子结合（GALE:NAD+二聚体）。GALE基因的缺陷可导致异构酶缺乏型半乳糖血症（EDG；MIM:230350），或称III型半乳糖血症（半乳糖代谢疾病），其临床特征包括早发性白内障、肝损伤、听力丧失和智力障碍。历史上，人们认为存在两种GALE缺乏的形式；一种是良性（“周围性”）形式，其中红细胞中不存在GALE活性，表现为轻微的症状（Gitzelmann 1972），另一种是罕见的“全身性”形式，所有组织中均无法检测到GALE活性，导致更严重的症状（Holton等，1981）。目前，该疾病被认为是一种连续体（Openo等，2006）。