Galactosemia is a carbohydrate metabolism disorder caused by inherited deficiencies in enzymes that convert galactose to glucose. Symptoms and signs include hepatic and renal dysfunction, cognitive deficits, cataracts, and premature ovarian failure. Diagnosis is by enzyme analysis of RBCs. Treatment is dietary elimination of galactose. Physical prognosis is good with treatment, but cognitive and performance parameters are often subnormal.
Galactose is found in dairy products, fruits, and vegetables. Autosomal recessive enzyme deficiencies cause 3 clinical syndromes.
This deficiency causes classic galactosemia. Incidence is 1/62,000 births; carrier frequency is 1/125. Infants become anorectic and jaundiced within a few days or weeks of consuming breast milk or lactose-containing formula. Vomiting, hepatomegaly, poor growth, lethargy, diarrhea, and septicemia (usually Escherichia coli) develop, as does renal dysfunction (eg, proteinuria, aminoaciduria, Fanconi syndrome), leading to metabolic acidosis and edema. Hemolytic anemia may also occur.
Without treatment, children remain short and develop cognitive, speech, gait, and balance deficits in their teenage years; many also have cataracts, osteomalacia (caused by hypercalciuria), and premature ovarian failure. Patients with the Duarte variant have a much milder phenotype.
There are benign and severe phenotypes. Incidence of the benign form is 1/23,000 births in Japan; no incidence data are available for the more severe form. The benign form is restricted to RBCs and WBCs and causes no clinical abnormalities. The severe form causes a syndrome indistinguishable from classic galactosemia, although sometimes with hearing loss.
Diagnosis of galactosemia is suggested clinically and supported by elevated galactose levels and the presence of reducing substances other than glucose (eg, galactose, galactose 1-phosphate) in the urine; it is confirmed by enzyme analysis of RBCs, hepatic tissue, or both. Most states require routine neonatal screening for galactose-1-phosphate uridyl transferase deficiency. (Also see testing for suspected inherited disorders of metabolism.)
Treatment of galactosemia is elimination of all sources of galactose in the diet, most notably lactose, which is a source of galactose present in all dairy products, including milk-based infant formulas and a sweetener used in many foods. A lactose-free diet prevents acute toxicity and reverses some manifestations (eg, cataracts) but may not prevent neurocognitive deficits. Many patients require supplemental calcium and vitamins. For patients with epimerase deficiency, some galactose intake is critical to ensure a supply of uridine-5′-diphosphate-galactose (UDP-galactose) for various metabolic processes.