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Test ID: GAL14 Galactosemia Gene Analysis (14-Mutation Panel)

Useful For

Second-tier test for confirming a diagnosis of galactosemia (indicated by enzymatic testing or newborn screening)

 

Carrier testing family members of an affected individual of known genotype (has mutations included in the panel)

 

Resolution of Duarte variant and Los Angeles (LA) variant genotypes

Testing Algorithm

Tests for the presence of the following 14 mutations in the GALT gene: -119_-116delGTCA, D98N, S135L, T138M, M142K, F171S, Q188R, L195P, Y209C, K285N, N314D, Q344K, c.253-2A>G, and 5 kb deletion.

 

See Galactosemia Testing Algorithm in Special Instructions.

Method Name

Multiplex Polymerase Chain Reaction (PCR)-Based Assay Utilizing the Agena Mass ARRAY Platform

Reporting Name

Galactosemia Gene Analysis

Specimen Type

Varies


Specimen Required


Specimen preferred to arrive within 96 hours of draw.

 

Submit only 1 of the following specimens:

 

Preferred:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Frozen/Refrigerated

 

Acceptable:

Specimen Type: Blood spot

Container/Tube: Whatman Protein Saver 903 Paper

Specimen Volume: 5 blood spots

Collection Instructions:

1. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.

2. Do not expose specimen to heat or direct sunlight.

3. Do not stack wet specimens.

4. Keep specimen dry.

Specimen Stability Information: Ambient (preferred)/Refrigerated


Specimen Minimum Volume

Blood: 1 mL; Blood Spots: 3

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

Classical galactosemia is an autosomal recessive disorder of galactose metabolism caused by mutations in the galactose-1-phosphate uridyltransferase (GALT) gene. The complete or near complete deficiency of the GALT enzyme is life threatening. If left untreated, complications include liver failure, sepsis, mental retardation, and death. Galactosemia is treated by a galactose-free diet, which allows for rapid 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 in 30,000.

 

Duarte variant galactosemia (compound heterozygosity for the Duarte mutation, N314D and -119_-116delGTCA in cis [on the same chromosome], and a classic mutation in trans [on the opposite chromosome]) is generally associated with higher levels of enzyme activity (5%-20%) than classic galactosemia (<5%); however, this may be indistinguishable by newborn screening assays. Typically, individuals with Duarte variant galactosemia have a milder phenotype but are also often treated with a low-galactose diet during infancy. The Los Angeles (LA) variant, which consists of N314D without the presence of -119_-116delGTCA, is associated with normal levels of GALT enzyme activity.

 

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, varies from state to state. The diagnosis of galactosemia is established by follow-up quantitative measurement of GALT enzyme activity. If enzyme levels are indicative of carrier or affected status, 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 mutations.

 

The GALT gene maps to 9p13. Several disease-causing mutations are common in patients with classic galactosemia (G/G genotype). The most frequently observed is the Q188R classic mutation. This mutation accounts for 60% to 70% of classical galactosemia alleles. The S135L mutation is the most frequently observed mutation in African Americans and accounts for approximately 50% of the mutant alleles in this population. The K285N mutation is common in those of eastern European descent and accounts for 25% to 40% of the alleles in this population. The L195P mutation is observed in 5% to 7% of classical galactosemia. The 5 kb deletion is common in individuals of Ashkenazi Jewish descent. The Duarte mutation (N314D and -119_-116delGTCA) is observed in 5% of the general United States population. The rest of the mutations detected by this method (ie, D98N, S135L, T138M, M142K, F171S, Y209C, and Q344K) are all uncommon, but known to be recurrent in the general population.

 

These mutations, in addition to the LA variant, are included in GAL14 / Galactosemia Gene Analysis (14-Mutation Panel) and in GCT / Galactosemia Reflex, Blood. See Galactosemia Testing Algorithm in Special Instructions for additional information. Refer to Galactosemia: Current Testing Strategy and Aids for Test Selection, Mayo Medical Laboratories Communique 2005 May;30(5) for more information regarding diagnostic strategy.

Reference Values

An interpretive report will be provided.

Interpretation

An interpretative report will be provided.

 

Results should be interpreted in the context of biochemical results.

Clinical Reference

1. Elsas LJ 2nd, Lai K: The molecular biology of galactosemia. Genet Med 1998 Nov-Dec;1(1):40-48

2. Kaye CI, Committee on Genetics, Accurso F, et al: Newborn screening fact sheets. Pediatrics 2006 Sep;118(3):e934-963

3. Novelli G, Reichardt JK: Molecular basis of disorders of human galactose metabolism: past, present, and future. Mol Genet Metab 2000 Sep-Oct;71(1-2):62-65

Day(s) and Time(s) Performed

Monday through Friday, Varies

Analytic Time

8 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81401-GALT (galactose-I-phosphate uridylyltransferase) (eg, galactosemia), full gene sequence

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GAL14 Galactosemia Gene Analysis In Process

 

Result ID Test Result Name Result LOINC Value
52878 Result Summary 50397-9
52879 Result 82939-0
52880 Interpretation 69047-9
52881 Specimen 31208-2
52882 Source 31208-2
52883 Method 49549-9
52884 Released By No LOINC Needed

Forms

1. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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