Galactosemia is an autosomal recessive disorder of galactose metabolism that often presents in the newborn period with poor suck, vomiting, diarrhea, bleeding diathesis, lethargy, jaundice, and sepsis. Approximately 10% of individuals also have cataracts. If left untreated, an individual may progress to irreversible liver disease and mental retardation.
Many affected infants are detected through state newborn screening programs near the time that they may become clinically symptomatic. For this reason, lactose should be removed from the diet of an affected infant while results of biochemical tests are pending. Infants born with classic galactosemia require lifelong dietary restriction of galactose, while variant galactosemia patients may not. Despite current treatment, affected individuals remain at risk for developmental delays, speech dyspraxia, and premature ovarian failure (females). The prevalence of galactosemia is approximately 1 in 30,000 newborns.
Galactosemia is most often caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT) enzyme, which catalyzes the production of glucose-1-phosphate and UDP-galactose from gal-1-P and UDP-glucose. The deficiency results in the accumulation of galactose-1-phosphate, galactose, and urine galactitol.
Comprehensive testing (GS) for galactosemia is accomplished by determining the GALT activity and the concentration of galactose-1-phosphate (gal-1-p).
Please note that if GALT gene sequencing (test code SG) is needed due to results from this test, DNA can be obtained from the sodium heparin (green top) tube submitted for this test.
There are two other enzymes in this biochemical pathway that when deficient can cause nonclassic (GALK) and UDP-galactose 4-epimerase (GALE). GALK and GALE deficiencies should be considered in patients who have an elevated gal-1-p concentration but normal GALT activity. Galactokinase deficiency should be considered in patients with cataracts and galactosemia who have an elevated gal-1-p but normal GALT activity. Epimerase deficiency should be considered in patients with liver disease, sensorineural deafness, failure to thrive and elevated gal-1-p but normal GALT activity.
This test is indicated in the case of:
- Follow up to abnormal newborn screening results
- Clinical symptoms of galactosemia
- Testing for siblings of an individual with galactosemia
For carrier screening, please order Galactosemia: Carrier Panel (GR).
GALT enzyme activity is performed using liquid chromatography – tandem mass spectrometry. Gal-1-P concentration is performed using a coupled enzymatic reaction detected by a spectrophotometric assay.
Detection and Reference Range
Diagnosis of galactosemia is made by measurement of GALT activity. Detection of reduced GALT activity is diagnostic for GALT deficient galactosemia.
Ranges of Gal-1-P uridyltransferase (GALT) activity (µmol/Hr/g Hb):
- Normal (N/N) 22.1 – 46.3
o Duarte galactosemia (D/G) 1.9 – 13.4
o Classic galactosemia (G/G) 0 – 0.3
Ranges for Galactose-1-Phosphate (RBC's):
- Normal: 0-1.0 mg/100 ml red blood cells
- Classic Galactosemia Therapeutic Range: <3.5 mg/ 100 mg red blood cells
Infants (Children (>2 years): 3-5 ml in both tubes
Older Children & Adults: 7-10 ml in both tubes
- Galactitol analysis is available and is the biochemical screening test for diagnosis and monitoring of patients with galactosemia.
- Galactosemia Carrier Testing is available through GALT enzyme activity.
- If the proband has a biochemical phenotype of galactosemia, GALT full gene sequencing is offered.
- GALT deletion/duplication analysis is offered when mutations are not detected by full gene sequencing.
- Prenatal testing is available by molecular methods. Please contact the laboratory genetic counselor to determine the availability of prenatal testing.