Galactosemia Gene Analysis, Known Mutation

CPT CODE:

USEFUL FOR:

Confirmation of diagnosis of galactosemia in a sibling or otherrelative of an individual with documented GALT mutations
Predictive testing of potential galactosemia carriers in families ofindividuals with documented GALT mutations

SPECIMEN REQUIRED:

This test can only be performed if a mutation has previously been identified in a family member of this individual. "Molecular Genetics - Biochemical Disorders Patient Information Sheet" (Supply T527 or see SpecialInstructions) is required for all orders. If not orderingelectronically, please submit the above information sheet alongwith a "Molecular Genetics Request Form" (Supply T245) with thespecimen. The name of the specific mutation in the family andthe laboratory at which testing was performed must be includedon the "Molecular Genetics - Biochemical Disorders PatientInformation Sheet" (Supply T527). Specimen must arrive within 96 hours of collection.  Submit 1 of the following specimens: BloodDraw blood in a lavender-top (EDTA) tube, and send 3 mL of EDTA whole blood in original VACUTAINER. Invert several times to mix blood. Forward unprocessed whole blood promptly at ambient temperature.
Prenatal SpecimensAll prenatal specimens must be accompanied by a maternalblood specimen. Due to the complexity of prenataltesting, consultation with the laboratory is required forall prenatal testing.
Amniotic FluidObtain 20 mL of amniotic fluid. Transfer specimen to 2 screw-capped, sterile centrifuge tubes. Send specimen refrigerated.Specimen cannot be frozen. A separate culture charge will beassessed under #80334 "Amniotic Fluid Culture for GeneticTesting." Alternatively, we will accept 2 T-25 flasks of confluentcultured cells from another laboratory sent at ambient temperature.
Chorionic VilliObtain 20 mg of chorionic villus specimen. Send specimenRefrigerated in transport media in 15-mL centrifuge tube.Specimen cannot be frozen. A separate culture charge willbe assessed under #80333 "Fibroblast Culture for GeneticTesting." Alternatively, we will accept 2 T-25 flasks of confluentcultured cells from another laboratory sent at ambienttemperature.

TRANSPORT TEMPERATURE:

VariesAmbient\Refrig OK\Frozen NO - BloodRefrig\Ambient OK\Frozen NO - Amniotic FluidRefrig\Ambient NO\Frozen NO - Chorionic Villi

CLINICAL INFORMATION:

Classic galactosemia is an autosomal recessive disease caused by mutations in the galactose-1-phosphate uridyltransferase gene (GALT).The complete or near complete deficiency of the galactose-1-phosphate uridyl transferase (GALT) enzyme is life threatening. If left untreated, complications include liver failure, sepsis, mental retardation, and neonatal death. Galactosemia is treated by a galactose-free diet, which allows for fast recovery from the acute symptoms and a generally good prognosis. Despite adequate treatment from an early age, children with galactosemia remain at increased risk for developmental delays, speech problems, and abnormalities of motor function. Females with galactosemia are at increased risk for premature ovarian failure. The prevalence of classic galactosemia is approximately 1/30,000.
Duarte variant galactosemia (compound heterozygosity for the Duartemutation, N314D, and a classic mutation) may mimic classic galactosemiain the biochemical assays used in newborn screening. Typically, Duartevariant galactosemia has a good prognosis, but is often treated with a lowgalactose diet during infancy. The Duarte variant (N314D) is found in 5%of the general United States population. The silent mutation (L218L), termed the Los Angeles or D1 Duarte variant, is uncommon and associated with increased GALT enzyme activity, but the biochemical phenotyping (by isoelectric focusing) is identical to that of Duarte variant.
Newborn screening, which identifies potentially affected individuals by measuring total galactose (galactose and galactose-1-phosphate) and/or determining the activity of the GALT enzyme deficiency varies fromstate to state. The diagnosis of galactosemia is established by quantitativemeasurement of GALT enzyme activity. If enzyme levels are indicative of carrier status or a diagnosis of galactosemia, molecular testing for common GALT mutations may be performed. If 1 or both disease-causing mutations are not detected by targeted mutation analysis and biochemical testing has confirmed the diagnosis of galactosemia, sequencing of the GALT gene is available to identify private mutation(s).
The GALT gene maps to 9p13 and has 11 exons. More than 180 mutationshave been identified in the GALT gene. Full sequencing of the GALT geneidentifies over 95% of the sequence variants in the coding region and splice junctions.
Several disease-causing mutations are commonly encountered in patientswith classic galactosemia:-The most fre

CLINICAL INTERPRETATION:

An interpretative report will be provided that includes an overview of the results and their significance, a correlation to available clinical information, elements of differential diagnosis, and recommendations for additional testing.
For diagnostic purposes, results should be interpreted in the context of biochemical results.

REFERENCE VALUES:

An interpretive report will be provided.