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 red blood cells and DNA analysis. Treatment is dietary elimination of galactose. Physical prognosis is good with treatment, but cognitive and performance parameters are often subnormal.
Galactose is present in dairy products, fruits, and vegetables. Autosomal recessive enzyme deficiencies cause 3 clinical syndromes.
See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism.
Galactose-1-phosphate uridyl transferase deficiency
This deficiency causes classic galactosemia. Incidence in the United States is approximately 1/50,000 births (1); 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 adolescence; many also have cataracts, osteomalacia (caused by hypercalciuria), and premature ovarian failure. Patients with the Duarte variant have a much milder phenotype.
Galactokinase deficiency
Patients develop cataracts from overproduction of galactitol, which osmotically damages lens fibers; idiopathic intracranial hypertension (pseudotumor cerebri) is rare.
Incidence is 1/40,000 births (2).
Uridine diphosphate galactose 4-epimerase deficiency
There are benign and severe phenotypes. Incidence of the benign form is 1/23,000 births in Japan (3); no incidence data are available for the more severe form.
The benign form is restricted to red and white blood cells and causes no clinical abnormalities.
The severe form causes a syndrome indistinguishable from classic galactosemia, although sometimes with hearing loss.
References
1. Sontag MK, Yusuf C, Grosse SD, et al. Infants with Congenital Disorders Identified Through Newborn Screening — United States, 2015–2017. MMWR Morb Mortal Wkly Rep 2020;69:1265–1268. doi:10.15585/mmwr.mm6936a6
2. Hennermann JB, Schadewaldt P, Vetter B, Shin YS, Mönch E, Klein J. Features and outcome of galactokinase deficiency in children diagnosed by newborn screening. J Inherit Metab Dis. 2011;34(2):399-407. doi:10.1007/s10545-010-9270-8
3. Misumi H, Wada H, Kawakami M, et al. Detection of UDP-galactose-4-epimerase deficiency in a galactosemia screening program. Clin Chim Acta. 1981;116(1):101-105. doi:10.1016/0009-8981(81)90173-x
Diagnosis of Galactosemia
Galactose levels
Enzyme analysis
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 DNA analysis or enzyme analysis of red blood cells, hepatic tissue, or both.
In the United States, all states require routine neonatal screening for galactose-1-phosphate uridyl transferase deficiency. (See also testing for suspected inherited disorders of metabolism.)
Treatment of Galactosemia
Dietary galactose restriction
Treatment of galactosemia is elimination of all sources of galactose in the diet, most notably lactose (a source of galactose), which is present in breast milk and in all dairy products, including milk-based infant formulas, and is 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.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man (OMIM) database: Complete gene, molecular, and chromosomal location information
