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Test ID GALZ Galactosemia, GALT Gene, Full Gene Analysis, Varies


Ordering Guidance


Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


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.

 

Submit only 1 of the following specimens:

 

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.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Cultured fibroblast

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or Blood Spot Collection Card

Specimen Volume: 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year of age is finger stick. See Dried Blood Spot Collection Tutorial for how to collect blood spots.

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

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

4. Do not stack wet specimens.

5. Keep specimen dry

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information:

1. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.

2. For collection instructions, see Blood Spot Collection Instructions

3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)

4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.


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 in Special Instructions:

-Informed Consent for Genetic Testing  (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

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

Useful For

Identifying variants in individuals who test negative for the common variants and who have a biochemical diagnosis of galactosemia or galactose-1-phosphate uridyltransferase activity levels indicative of carrier status

Testing Algorithm

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

 

See Galactosemia Testing Algorithm .

Method Name

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

Reporting Name

Galactosemia, Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

Classic galactosemia is an autosomal recessive disorder of galactose metabolism caused by 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. 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 variant, N314D and a classic variant) is generally associated with higher levels of GALT 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 often treated with a low galactose diet during infancy. The LA variant, consisting of N314D and a second change, L218L, is associated with higher levels of GALT activity than the Duarte variant alone.

 

Newborn screening, which identifies potentially affected individuals by measuring total galactose (galactose and galactose-1-phosphate) 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 activity. If enzyme activity levels are indicative of carrier or affected status, molecular testing for common GALT variants may be performed. If 1 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 and more than 180 variants have been identified. Several disease-causing variants are common in patients with classic galactosemia (G/G genotype). The most frequently observed is the Q188R variant, which accounts for 60% to 70% of classic galactosemia alleles. The S135L variant is the most frequently observed variant in the African American population 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 classic galactosemia. The Duarte variant (N314D) is found in 5% of the general United States population.

 

The above variants, plus the LA variant, are included in GCT / Galactosemia Reflex, Blood, which is the preferred test for the diagnosis of galactosemia or for follow-up to positive newborn screening results. These variants are also included in GAL14 / Galactosemia Gene Analysis (14-Variant Panel), Varies. Full sequencing of the GALT gene can be useful for the identification of variants when 1 or no variants are found with these tests in an individual with demonstrated GALT activity deficiency. Full sequencing of the GALT gene identifies over 95% of the sequence variants in the coding region and splice junctions. See Galactosemia Testing Algorithm in Special Instructions for additional information. 

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

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

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

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

4. Bosch AM, Ijlst L, Oostheim W, et al: Identification of novel variants in classical galactosemia. Hum Mutat. 2005 May;25(5):502 

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

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

81406

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GALZ Galactosemia, Full Gene Analysis 76037-1

 

Result ID Test Result Name Result LOINC Value
608596 Test Description 62364-5
608597 Specimen 31208-2
608598 Source 31208-2
608599 Result Summary 50397-9
608600 Result 82939-0
608601 Interpretation 69047-9
608602 Resources 99622-3
608603 Additional Information 48767-8
608604 Method 85069-3
608605 Genes Analyzed 48018-6
608606 Disclaimer 62364-5
608607 Released By 18771-6

Day(s) Performed

Varies

Report Available

4 to 6 weeks

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No