Newborn screening · Other inherited disorder
Classic Galactosemia · GALT
GALT enzyme deficiency. Lactose-free formula prevents acute neonatal liver failure. Long-term outcomes are mixed.
Description
Classic galactosemia is an autosomal recessive disorder of carbohydrate metabolism. Pathogenic variants in GALT reduce or abolish galactose-1-phosphate uridyltransferase activity. Dietary galactose, supplied chiefly as lactose in milk, is then not metabolized on the normal pathway, and galactose-1-phosphate and related metabolites accumulate in blood and tissues. Inheritance is autosomal recessive. The causative gene is GALT on chromosome 9.
Affected newborns often present in the first one to two weeks of life with feeding intolerance, vomiting, poor weight gain, jaundice, and hepatomegaly. Untreated disease progresses to liver failure and gram-negative sepsis, classically Escherichia coli. Galactosemic cataracts can develop when exposure continues.
Detection is by newborn screening on the dried blood spot. State programs use enzyme activity assays, total galactose measurement, or both. Confirmation uses red-cell GALT enzyme activity and GALT gene sequencing. The Duarte biochemical variant reflects partial enzyme activity and is managed separately from classic deficiency.
Reported live-birth incidence in Western newborn screening programs is approximately 1 in 40,000 to 1 in 60,000. Founder populations show elevated rates. Murphy et al. (Human Genetics, 1999) estimated classical galactosemia incidence among Irish Travellers at about 1 in 480 births compared with about 1 in 30,000 among non-Traveller Irish births. Coss et al. (Journal of Inherited Metabolic Disease, 2013) reported a blended Irish live-birth incidence near 1 in 16,500.
Treatments to date
Treatment is lifelong dietary restriction of lactose and galactose, started as soon as classic galactosemia is suspected after newborn screening or clinical presentation. Soy-based or elemental lactose-free formulas replace breast milk or standard cow milk formula in infancy. Restriction continues through childhood and adulthood. A metabolic dietitian monitors calorie adequacy, protein intake, calcium, and vitamin D.
During acute illness, standard metabolic emergency protocols apply. Neonatal sepsis surveillance accompanies the first weeks of treatment because risk of Escherichia coli sepsis is elevated before dietary correction takes effect.
No approved enzyme replacement therapy or small-molecule therapy restores normal GALT activity. Gene therapy and substrate reduction approaches exist only within regulated trials.
Long-term complications develop in many people with classic galactosemia despite early dietary control. Learning differences, speech apraxia, and motor coordination problems appear in substantial fractions of cohorts in Irish national outcome reviews and international registry summaries. Premature ovarian insufficiency or hypergonadotropic hypogonadism develops in almost all females with classic galactosemia in major longitudinal cohorts. Reduced bone density is also reported. Lens examination remains part of routine follow-up.