Galactosemia is a disorder of galactose metabolism that can result in life-threatening complications including feeding problems, failure to thrive, hepatocellular damage, bleeding, and sepsis in untreated infants. If a lactose/galactose-restricted diet is provided during the first ten days of life, the neonatal symptoms quickly resolve and the complications of liver failure, sepsis, neonatal death, and intellectual disability can be prevented. Despite adequate treatment from an early age, children with galactosemia remain at increased risk for developmental delays, speech problems (termed "verbal dyspraxia"), and abnormalities of motor function. A female with galactosemia is at increased risk for premature ovarian insufficiency.
The diagnosis of galactosemia is established by measurement of erythrocyte galactose-1-phosphate uridyltransferase (GALT) enzyme activity, erythrocyte galactose-1-phosphate (gal-1-P) concentration, and GALT molecular genetic testing. In classic (G/G) galactosemia, GALT enzyme activity is less than 5% of control values and erythrocyte gal-1-P is higher than 10 mg/dL; in Duarte variant (D/G) galactosemia, GALT enzyme activity is usually higher 5% and approximates 25% of control values. Molecular genetic testing of GALT, the gene encoding galactose-1-phosphate uridyltransferase, is clinically available. Virtually 100% of affected infants can be detected in states that include testing for galactosemia in their newborn screening programs.
Galactosemia is inherited in an autosomal recessive manner. Couples who have had one affected child have a 25% chance of having an affected child in each subsequent pregnancy. Prenatal diagnosis is possible for pregnancies at 25% risk for classic galactosemia using molecular genetic testing if the disease-causing GALT mutations in the family are known. If the disease-causing GALT mutations in a family are not known, GALT enzyme activity may be assayed in cultured amniotic fluid cells.