Classic galactosemia is a rare inborn error of metabolism that affects the metabolism of galactose, a sugar derived from milk and derivates. Classic galactosemia is caused by variants of the GALT gene, which lead to absent or misfolded forms of the ubiquitously present galactose-1-phosphate uridylyltransferase enzyme (GALT) driving galactose metabolites to accumulate, damaging cells from neurons to hepatocytes. The disease has different prevalence around the world due to different allele frequencies among populations and its symptoms range from cognitive and psychomotor impairment to hepatic, ophthalmological, and bone structural damage. The practice of newborn screening still varies among countries, dairy restriction treatment is a consensus despite advances in preclinical treatment strategies. Recent clinical studies in Duarte variant suggest dairy restriction could be reconsidered in these cases. Despite noteworthy advances in the classic galactosemia understanding, preclinical trials are still crucial to fully understand the pathophysiology of the disease and help propose new treatments. This review aims to report a comprehensive analysis of past studies and state of art research on galactosemia screening, its clinical and preclinical trials, and treatments with the goal of shedding light on this complex and multisystemic innate error of the metabolism.

经典的半乳糖血症是一种罕见的先天性代谢错误，会影响半乳糖（一种从牛奶及其衍生物中提取的糖）的代谢。经典的半乳糖血症是由GALT基因的变异引起的，这种变异会导致普遍存在的 1-磷酸半乳糖尿苷酰转移酶 (GALT) 缺失或错误折叠，从而驱动半乳糖代谢物积累，从而损害从神经元到肝细胞的细胞。由于人群中等位基因频率不同，该疾病在世界各地的患病率不同，其症状范围从认知和精神运动障碍到肝脏、眼科和骨结构损伤。各国新生儿筛查的做法仍然存在差异，尽管临床前治疗策略取得了进展，但限制乳制品治疗已成为共识。最近针对杜阿尔特变种的临床研究表明，在这些病例中可以重新考虑限制乳制品。尽管对经典半乳糖血症的认识取得了显着进展，但临床前试验对于充分了解该疾病的病理生理学并帮助提出新的治疗方法仍然至关重要。本综述旨在对半乳糖血症筛查、临床和临床前试验以及治疗的过去研究和最新研究进行全面分析，旨在阐明这种复杂的多系统先天性代谢错误。