Test ID: GBAZ Gaucher Disease, Full Gene Analysis, Varies
Useful For
Confirmation of a diagnosis of Gaucher disease
Carrier screening in cases where there is a family history of Gaucher disease, but an affected individual is not available for testing or disease-causing alterations have not been identified
Genetics Test Information
Testing includes full gene sequencing of the GBA gene.
Risk alleles for Parkinson disease with no known beta-glucocerebrosidase enzyme reduction or Gaucher disease association will only be reported in patients over 18 years old unless otherwise requested.
Reflex Tests
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
CULFB | Fibroblast Culture for Genetic Test | Yes | No |
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.
For more information see Newborn Screen Follow-up for Gaucher Disease.
If the patient has abnormal newborn screening results for Gaucher disease, refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet.(1)
Method Name
Polymerase Chain Reaction (PCR) followed by DNA Sequencing
Reporting Name
Gaucher Disease, Full Gene AnalysisSpecimen Type
VariesOrdering Guidance
This is not the preferred genetic test for carrier screening or diagnosis in individuals of Ashkenazi Jewish ancestry. For these situations, order GAUP / Gaucher Disease, Mutation Analysis, GBA, Varies.
For diagnostic testing in potentially affected individuals, enzyme testing should be performed prior to molecular genetic analysis. Order GBAW / Beta-Glucosidase, Leukocytes.
For ongoing therapeutic monitoring, order GPSY / Glucopsychosine, Blood Spot.
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 specimen in original tube.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Specimen Type: Cultured fibroblasts
Container/Tube: T-75 or T-25 flask
Specimen Volume: 1 Full T-75 or 2 full T-25 flasks
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: 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: 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: 2 to 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.
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 Minimum Volume
Blood: 1 mL
Blood Spots: 5 punches, 3-mm diameter
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Varies |
Clinical Information
Gaucher disease is a relatively rare lysosomal storage disorder resulting from a deficiency of acid beta-glucocerebrosidase. Reduced or absent activity of this enzyme results in accumulation of its substrate in lysosomes, interfering with cell function. There are 3 major types of Gaucher disease: nonneuropathic (type 1), acute neuropathic (type 2), and subacute neuropathic (type 3). In addition, there are 2 rare presentations of Gaucher disease: a perinatal lethal form associated with skin abnormalities and nonimmune hydrops fetalis, and a cardiovascular form presenting with calcification of the aortic and mitral valves, mild splenomegaly, and corneal opacities. Gaucher disease demonstrates large clinical variability, even within families.
Type 1 accounts for over 95% of all cases of Gaucher disease and is the presentation commonly found among Ashkenazi Jewish patients. The carrier rate of Gaucher disease in the Ashkenazi Jewish population is 1:18. There is a broad spectrum of disease in type 1 Gaucher disease, with some patients exhibiting severe symptoms and others very mild disease. Type 1 disease does not involve nervous system dysfunction; patients may display anemia, low blood platelet levels, massively enlarged livers and spleens, lung infiltration, and extensive skeletal disease. Type 2 is characterized by early-onset neurologic disease with rapid progression to death by 2 to 4 years of age. Type 3 may have early onset of symptoms, but generally a slower disease progression than type 2.
Alterations in the GBA gene cause the clinical manifestations of Gaucher disease. Over 250 variants have been reported to date. The N370S and L444P alterations have the highest prevalence in most populations. N370S is associated with type 1 Gaucher disease, and individuals with at least 1 copy of this alteration do not develop the primary neurologic disease seen in types 2 and 3. Conversely, L444P is associated with neurologic disease.
Alterations in the GBA gene have also been reported to cause an increased risk for Parkinson disease. Alterations associated with Parkinson disease, but not Gaucher disease, are not routinely reported for patients under the age of 18, but are available upon request.
For carrier screening of the general population, the recommended test is GAUP / Gaucher Disease, Mutation Analysis, GBA, Varies, which tests for the 8 most common GBA alterations. For diagnostic testing (ie, potentially affected individuals), enzyme testing (GBAW / Beta-Glucosidase, Leukocytes) should be performed prior to variant analysis. In individuals with abnormal enzyme activity and 1 or no variants detected by a panel of common alterations, sequence analysis of the GBA gene should be utilized to detect private variants. Additionally, measurement of the glucopsychosine biomarker can aid in diagnosis and ongoing therapeutic monitoring (GPSY / Glucopsychosine, Blood Spot).
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.(2) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Newborn Screening ACT Sheet [Decreased beta-glucocerebrosidase] Gaucher Disease. American College of Medical Genetics and Genomics; 2022. Revised March 2022. Accessed June 10, 2024. Available at www.acmg.net/PDFLibrary/Gaucher.pdf
2. 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
3. Guggenbuhl P, Grosbois B, Chales G: Gaucher disease. Joint Bone Spine. 2008 Mar;75(2):116-124
4. Hruska KS, LaMarca ME, Scott CR, Sidransky E: Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat. 2008 May;29(5):567-583
5. O'Regan G, deSouza RM, Balestrino R, Schapira AH: Glucocerebrosidase mutations in Parkinson disease. J Parkinsons Dis. 2017;7(3):411-422
Day(s) Performed
Varies
Report Available
14 to 20 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81479-Unlisted molecular pathology procedure code
88233-Tissue culture, skin, or solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
GBAZ | Gaucher Disease, Full Gene Analysis | 94230-0 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
53477 | Result Summary | 50397-9 |
53478 | Result | 82939-0 |
53479 | Interpretation | 69047-9 |
53480 | Additional Information | 48767-8 |
53481 | Specimen | 31208-2 |
53482 | Source | 31208-2 |
53483 | Released By | 18771-6 |
Forms
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
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