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Test ID GALMP Galactosemia, GALT Gene, Variant Panel, Varies


Ordering Guidance


The recommended as a first-tier test is galactose-1-phosphate uridyltransferase enzyme analysis; order GALT / Galactose-1-Phosphate Uridyltransferase, Blood.

 

This genetic variant panel is recommended for individuals with a GALT enzyme value less than 24.5 nmol/h/mg of hemoglobin.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


Multiple whole blood tests for galactosemia can be performed on one specimen. Prioritize order of testing when submitting specimens. See Galactosemia-Related Test List for a list of tests that can be ordered together.

 

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

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 whole blood specimen in original tube. Do not aliquot.


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527)

Useful For

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

 

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

 

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

Testing Algorithm

For more information see Galactosemia Testing Algorithm

Method Name

Targeted Genotyping Array

Reporting Name

Galactosemia Mutation Panel

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

Classical galactosemia is an autosomal recessive disorder of galactose metabolism caused by genetic variants 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, intellectual disability, 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. Women 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 variant, N314D and -119_-116delGTCA in cis [on the same chromosome], and a classic variant 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 variants may be performed. If one or both disease-causing variants are not detected by targeted variant analysis and biochemical testing has confirmed the diagnosis of galactosemia, sequencing of the GALT gene is available to identify private variants.

 

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

 

These variants, in addition to the LA variant, are included in this test and in GCT / Galactosemia Reflex, Blood. For more information see Galactosemia Testing Algorithm.

 

Table. Targeted Variants

Associated phenotype

Gene (transcript)

Variants

Galactosemia

GALT (NM_000155)

c.-119_-116del*, c.136_140del, c.221T>C*, c.253-2A>G*, c.292G>A*, c.404C>T*, c.413C>T*, c.425T>A*, c.443G>A*, c.505C>A, c.512T>C*, c.563A>G*, c.584T>C*, c.607G>A*, c.626A>G*, c.855G>T*, c.940A>G*, c.958G>A*, c.997C>G*, c.997C>T*, c.1018G>T, c.1030C>A*, c.1138T>C*
Deletion analysis of exon 1-11

 

*Previously detected in a known positive sample

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.

 

If results of the galactose-1-phosphate uridyltransferase enzyme analysis and this test are discordant, then consider GALZ / Galactosemia, GALT Gene, Full Gene Analysis, Varies.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424. doi: 10.1038/gim.2015.30

2. Elsas LJ 2nd, Lai K: The molecular biology of galactosemia. Genet Med. 1998 Nov-Dec;1(1):40-48. doi: 10.1097/00125817-199811000-00009

3. Kaye CI, Committee on Genetics, Accurso F, et al: Newborn screening fact sheets. Pediatrics. 2006 Sep;118(3):e934-e963. doi: 10.1542/peds.2006-1783

4. 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. doi: 10.1006/mgme.2000.3073

5. Welling L, Bernstein LE, Berry GT, et al: International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up. J Inherit Metab Dis. 2017 Mar;40(2):171-176. doi: 10.1007/s10545-016-9990-5

6. Carlock G, Fischer ST, Lynch ME, et al: Developmental outcomes in Duarte galactosemia. Pediatrics. 2019 Jan;143(1):e20182516. doi: 10.1542/peds.2018-2516

Day(s) Performed

Thursday, Sunday

Report Available

7 to 21 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 US Food and Drug Administration.

CPT Code Information

81401

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GALMP Galactosemia Mutation Panel 42318-6

 

Result ID Test Result Name Result LOINC Value
606344 Result Summary 50397-9
606345 Result 82939-0
606346 Interpretation 69047-9
606347 Additional Information 48767-8
606348 Method 85069-3
606349 Specimen 31208-2
606350 Source 31208-2
606351 Released By 18771-6