Master's in Genetic Counseling (MGC)
Galactosemia
Galactosemia is an autosomal recessive disorder resulting from a deficiency in one of the three enzymes responsible for the metabolism of galactose (galactokinase, epimerase, or galactose-1-phosphate uridyl transferase[GAL-1-PUT]). Galactose is one of the two monosaccharides which make up lactose, the predominant carbohydrate in human and other animal milk.
Clinical Features
Infants with classic GAL-1-PUT-deficient galactosemia may appear normal at birth. Within a few days to weeks after milk feeding is initiated, however, the clinical features will begin to develop. Symptoms may consist of vomiting, diarrhea, lethargy, failure to thrive, jaundice, hypoglycemia and sepsis. Without rapid diagnosis and treatment, death may result . If the infant survives the neonatal period but continues untreated, progressive mental retardation, growth failure, cataracts, hepatomegaly, Fanconi syndrome, and motor retardation may result. (OMIM)
Galactokinase deficiency may manifest with cataracts in the neonatal period. The other symptoms of GAL-1-PUT deficiency are not present. Galactokinase deficiency should be considered in infants with a normal GAL-1-PUT assay along with elevated galactose levels. (OMIM)
Epimerase deficiency, occurring most commonly in the African American population, is an apparently benign condition. It should also be considered as a possible cause for a normal GAL-1-PUT assay in conjunction with elevated galactose levels. (OMIM)
Laboratory Tests
Screening for galactosemia may involve a variety of tests. One test, known as the Beutler assay, consists of a fluorometric assay that determines the activity of the enzyme galactose-1-phosphate uridyl transferase (GAL-1-PUT). The Beutler test is considered abnormal if little or no fluorescence is observed, indicating little or reduced enzyme activity. Absent activity may indicate an individual with possible classic (GAl-1-PUT deficient) galactosemia. A second screening test is designed to detect the level of galactose in the blood. This is accomplished through a bacterial inhibition assay (the Paigen test) or a fluorometric assay (the Hill test). A normal Beutler assay for GAL-1-PUT and elevated galactose levels may be indicative of a mild galactosemia variant, galactokinase deficiency, or epimerase deficiency. Follow-up for abnormal galactosemia screens may consists of obtaining urine for reducing substances with subsequent referral to a genetic/metabolic consultant for those with positive reducing substances. Diagnostic tests may include a quantitative transferase, kinase, and epimerase assay in addition to quantitative galactose and galactose-1-phosphate levels.
Note: Untreated classic (GAL-1-PUT deficient) galactosemia may be rapidly fatal and requires immediate follow up.
Treatment
Management of galactosemia consists of excluding lactose and galactose from the diet. A soy based formula is most often used. A product such as “Lactaid” is not sufficient to eliminate galactose from the diet. Elimination of milk and milk products is also not sufficient for this diet, as galactose is present in other foods. A pediatric metabolic specialist and nutritionist are necessary for educating parents about foods that are appropriate for this diet. Dietary restriction should be continued indefinitely, and close supervision and monitoring are necessary.
Dietary exclusion of galactose will reduce the clinical severity of the symptoms associated with galactosemia. However, the diet does not ensure full normalcy as galactose can be produced by the body from glucose. Affected individuals may still experience speech and language difficulties, mental decline, hyperactivity, and premature ovarian failure in females. For specific management guidelines, please refer the patient to a genetic/metabolic specialist.
Screening Practice Considerations
The Beutler test for GAL-1-PUT activity does not depend on lactose ingestion for accuracy. However, it is very important that the specimen is obtained before any transfusions, as this may produce a false negative result. If classic galactosemia is suspected clinically, dietary restriction of galactose should begin immediately, as this will not affect the detection of GAL-1-PUT activity. If a patient has received a transfusion prior to specimen collection, a specimen should be obtained 90 to 120 days following the last transfusion. It is also possible to test the parents in order to determine their carrier status. Again, if classic galactosemia is a clinical consideration, these infants can be maintained on a galactose free formula until accurate testing is complete.
The screening tests designed to detect galactose levels do depend on lactose ingestion. Galactose levels will appear normal in affected infants that have not had adequate lactose ingestion or are consuming non-lactose containing formulas.
Click on a state below for state specific follow-up procedures.
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