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HelpTest Code LGB3S Globotriaosylsphingosine, Serum
Reporting Name
Lyso-GB3, SUseful For
Diagnosis and monitoring of Fabry disease
Testing Algorithm
The following algorithms are available:
-Fabry Disease: Newborn Screen-Positive Follow-up
-Fabry Disease Diagnostic Testing Algorithm
Method Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
SerumOrdering Guidance
This test should not be used to determine carrier status. Order FABRZ / Fabry Disease, Full Gene Analysis, Varies for carrier testing.
Necessary Information
1. Patient's age is required.
2. Reason for testing is required.
Specimen Required
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Specimen Minimum Volume
0.5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Frozen (preferred) | 90 days | |
| Refrigerated | 48 hours |
Reject Due To
| Gross hemolysis | OK |
| Gross lipemia | Reject |
| Gross icterus | OK |
Special Instructions
Reference Values
≤1.0 ng/mL
Day(s) Performed
Thursday
CPT Code Information
82542
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| LGB3S | Lyso-GB3, S | 90234-6 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| BG708 | Reason for Referral | 42349-1 |
| 65532 | Lyso-GB3, S | 90234-6 |
| 113176 | Interpretation (LGB3S) | 59462-2 |
| 113177 | Reviewed By | 18771-6 |
Forms
1. Biochemical Genetics Patient Information (T602)
2. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Secondary ID
65532Clinical Information
Fabry disease is an X-linked recessive lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A (alpha-Gal A). Reduced enzyme activity results in accumulation of glycosphingolipids in the lysosomes throughout the body, in particular, the kidney, heart, and brain. Severity and onset of symptoms are dependent on the residual enzyme activity. Symptoms may include acroparesthesias (pain crises), multiple angiokeratomas, reduced or absent sweating, corneal opacity, renal insufficiency leading to end-stage kidney disease, and cardiac and cerebrovascular disease. There are renal and cardiac variant forms of Fabry disease that may be underdiagnosed. Female patients who are carriers of Fabry disease can have clinical presentations ranging from asymptomatic to severely affected, and they may have alpha-Gal A activity in the normal range. The estimated incidence varies from 1 in 3000 infants detected via newborn screening to 1 in 10,000 male patients diagnosed after onset of symptoms.
Unless irreversible damage has already occurred, treatment with enzyme replacement therapy leads to significant clinical improvement in affected individuals. For this reason, early diagnosis and treatment are desirable. In a few US states, early detection of Fabry disease through newborn screening has been implemented.
Absent or reduced alpha-Gal A in blood spots, leukocytes (AGAW / Alpha-Galactosidase, Leukocytes), or serum (AGAS / Alpha-Galactosidase, Serum) can indicate a diagnosis of classic or variant Fabry disease. Molecular sequence analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis, Varies) allows for detection of the disease-causing variant in male and female patients. Molecular genetic testing is the recommended diagnostic test for female patients as alpha-galactosidase activity may be in the normal range in those affected.
The glycosphingolipid, globotriaosylsphingosine (LGb3), may be elevated in symptomatic patients and supports a diagnosis of Fabry disease. It may also be helpful as a tool for monitoring disease progression as well as determining treatment response in known patients. In addition, measurement of LGb3, may provide additional diagnostic information in the evaluation of uncertain cases, such as in asymptomatic heterozygous female patients, individuals with novel GLA variants of unclear clinical significance, as well as asymptomatic patients identified by family screening.
Interpretation
Elevation of globotriaosylsphingosine is diagnostic for Fabry disease.
Cautions
Carrier detection using globotriaosylsphingosine (LGb3) is unreliable.
Some patients with Fabry disease may, and all individuals with pseudodeficiency of alpha-galactosidase enzyme, have normal concentrations of LGb3.
Clinical Reference
1. Aerts JM, Groener JE, Kuiper S, et al: Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci USA. 2008 Feb 26;105(8)2812-2817
2. Mehta A, Hughes DA: Fabry disease. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2002. Updated January 27, 2022. Accessed January 17, 2023. Available at www.ncbi.nlm.nih.gov/books/NBK1292/
3. Laney DA, Bennett RL, Clarke V, et al: Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2013 Oct;22(5):555-564
4. Laney DA, Peck DS, Atherton AM, et al: Fabry disease in infancy and early childhood: a systematic literature review. Genet Med. 2015 May;17(5):323-330
5. Weidemann F, Beer M, Kralewski M, Siwy J, Kampmann C: Early detection of organ involvement in Fabry disease by biomarker assessment in conjunction with LGE cardiac MRI: results from the SOPHIA study. Mol Genet Metab. 2019 Feb;126(2):169-182
Method Description
Internal standard is added to the serum. Globotriaosylsphingosine (LGb3) is extracted from the serum prior to injection onto a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. Following chromatographic isolation, the concentration is measured by MS/MS analysis in the selected reaction monitoring positive mode. The ratio of extracted peak area to internal standard is utilized to calculate the concentration of LGb3 in the sample.(Unpublished Mayo method)