Indications for Testing
Testing for classic galactosemia is included in mandated newborn screening panels throughout the U.S. Newborns with abnormal screening test results for galactosemia should undergo further testing. Individuals with a family history of galactosemia or patients with symptoms of galactosemia (see Quick Answers above) also warrant testing. Carrier testing is indicated in parents and family members of affected children.
Testing of GALT enzyme activity in red blood cells is indicated in patients with newborn screening results that suggest classic galactosemia (and in those with family history or symptoms of the disease). GALT activity is absent or greatly reduced in affected patients (<0.20 U/Hb in red blood cells); a GALT activity of ≤3% of normal is diagnostic for classic galactosemia.
Measurement of GALT activity in red blood cells after blood transfusion can cause false-negative results, as GALT activity in donor blood is detectable for up to 4 months after a transfusion. DNA analysis or measurement of galactose metabolites can be useful to confirm or rule out the possibility of galactosemia in transfused patients, as can parental testing. (See Molecular Tests and Metabolite Assays below.)
DNA analysis to detect common pathogenic variants in GALT is often part of the evaluation of patients with suspected classic galactosemia. Other molecular tests that may be useful include GALT gene sequencing or targeted deletion/duplication tests, particularly if the results of biochemical tests are equivocal. Follow-up molecular testing of parents of an affected child can help assess risk associated with future pregnancies.
For more information on GALT variants and polymorphisms, refer to ARUP's GALT gene database. Genotype/phenotype correlations aid in prognostication. Test options for genotype/phenotype determination include targeted mutation panels and full gene sequencing (see Additional Technical Information, Galactosemia (GALT) Enzyme Activity and 9 Mutations).
Galactose-1-phosphate is a galactose metabolite that can be measured in patients with suspected galactosemia. Patients with classic galactosemia who have not yet received treatment (ie, removal of dietary galactose) will have high concentrations of galactose-1-phosphate in red blood cells.
Galactitol, another metabolite, can be measured in urine or in red blood cells (testing not performed at ARUP Laboratories); urinary galactitol is increased in individuals with classic galactosemia, although baseline values may vary widely among patients.
Concentrations of galactose-1-phosphate in red blood cells are typically monitored in patients with galactosemia, and a correlation exists between these concentrations and long-term outcome. Urinary galactitol concentrations may also be helpful for monitoring.
Patients with classic galactosemia should be monitored for long-term complications, including cognitive, psychosocial, neurologic, and speech and language complications, and changes in bone health and fertility in girls/women. In girls/women, follicle-stimulating hormone, luteinizing hormone, estradiol, and anti-Mullerian hormone are useful to assess reproductive function.