Galactosemia

Galactosemia is a rare inherited metabolic disorder characterized by the body's inability to properly metabolize galactose, a sugar found in milk and dairy products. The condition most commonly results from deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT), but can also be caused by deficiency of galactokinase (GALK) or galactose-6-phosphate epimerase (GALE). These defects disrupt the Leloir pathway, causing accumulation of galactose and galactose-1-phosphate and reduced synthesis of UDP-glucose.

Classic galactosemia (GALT deficiency) presents in newborns with poor feeding, vomiting, jaundice, hepatomegaly, lethargy, and failure to thrive and may progress to liver failure or sepsis if untreated. GALK deficiency commonly causes galactitol buildup leading to cataracts but minimal acute metabolic illness. GALE deficiency has a broad spectrum, from mild to severe, with variable symptoms including metabolic instability or cataracts. Long-term complications in classic galactosemia can include speech and motor delays, cognitive impairment, and, in females, ovarian insufficiency.

Newborn screening may detect low GALT activity or elevated galactose or galactose-1-phosphate; confirmation involves measurement of enzyme activities in red blood cells and genetic testing of GALT, GALK, and GALE genes. Additional tests assess liver function and growth; differential diagnosis includes other causes of neonatal liver disease.

Management requires strict lifelong restriction of lactose and galactose from the diet, using soy-based formulas for infants and avoiding breast milk and dairy products. Early treatment improves outcome but does not eliminate risk of complications. Supportive care includes infection prevention and prompt treatment, regular monitoring of growth, development, and liver function, and management of cataracts or ovarian problems as they arise. GALK deficiency treatment focuses on cataract management; there is no specific diet change beyond dietary galactose restriction.

Galactosemia is inherited in an autosomal recessive manner. Affected individuals have two mutant alleles. Prognosis improves with early detection and treatment; some neurodevelopmental or reproductive issues may persist despite therapy.