Pathophysiology
Clinical meaning
Galactosemia is an autosomal recessive inborn error of metabolism in which the body cannot properly metabolize galactose, a simple sugar that is a component of lactose (the primary carbohydrate in breast milk and cow's milk formula). Lactose is a disaccharide composed of glucose and galactose; it is broken down by the enzyme lactase in the small intestine into its two component monosaccharides. In normal metabolism, free galactose undergoes a three-step enzymatic conversion known as the Leloir pathway to ultimately be converted to glucose-1-phosphate, which can enter glycolysis for energy production. The three enzymes in this pathway are galactokinase (GALK), galactose-1-phosphate uridylyltransferase (GALT), and UDP-galactose-4-epimerase (GALE). Classic galactosemia, the most severe form, results from a deficiency of the GALT enzyme due to mutations in the GALT gene on chromosome 9p13. When GALT is deficient or absent, galactose-1-phosphate and galactitol (an alternative metabolite produced by aldose reductase) accumulate in tissues throughout the body, producing toxic effects on multiple organ systems. In the liver, galactose-1-phosphate accumulation causes hepatocellular damage leading to hepatomegaly, jaundice, and potentially cirrhosis and liver failure. The accumulation inhibits glucose...