Abstract

Classic Galactosemia (CG) is an autosomal recessive disorder caused by mutations in the galactose-1-phosphate uridyltransferase (GALT) gene, leading to disruptions in the Leloir pathway of galactose metabolism. The buildup of galactose and its metabolites, such as galactitol and galactonate, contributes to a wide range of clinical manifestations, including liver disease, neurological impairment, and ovarian insufficiency. This paper explores the biochemical mechanisms underpinning CG, its pathophysiology, diagnosis, and clinical impact of GALT mutations. The study presents data from a recent multicenter cohort analysis, showing that the Q188R mutation is associated with a significantly higher prevalence of cognitive impairment (75%, p < 0.01) and ovarian insufficiency (50%, p < 0.05) compared to the S135L (20% and 10%) and N314D (15% and 5%) mutations. These findings suggest that genotype plays a critical role in the severity of CG and patient outcomes. Early diagnosis and dietary intervention are crucial, but research indicates that some complications persist even with treatment. This review emphasizes the need for further therapeutic advances to improve patient outcomes.