Diagnosing and monitoring of patients with Fabry disease when a serum specimen is not available
This test is not intended for newborn screening followup.
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Whole blood
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Green top (sodium heparin, lithium heparin) and yellow top (ACD B)
Specimen Volume: 1 mL
0.25 mL
Gross hemolysis | OK |
Gross lipemia | OK |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Whole blood | Refrigerated (preferred) | 72 hours | |
Ambient | 48 hours |
Diagnosing and monitoring of patients with Fabry disease when a serum specimen is not available
This test is not intended for newborn screening followup.
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, kidney 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 heterozygous for 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 has led to significant clinical improvement in affected individuals. For this reason, early diagnosis and treatment are desirable, and in a few states, early detection of Fabry disease through newborn screening has been implemented.
Measurement of alpha-GAL A in leukocytes (AGAW / Alpha-Galactosidase, Leukocytes), serum (AGAS / Alpha-Galactosidase, Serum), or blood spots (AGABS / Alpha-Galactosidase, Blood Spot) can reliably diagnose classic or variant Fabry disease in male patients. Molecular genetic testing is the recommended diagnostic test for female patients as alpha-GAL A may be in the normal range in an affected female patient. Molecular analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis, Varies) allows for detection of the disease-causing variant in both male and female patients.
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.
Cutoff: < or =0.034 nmol/mL
An elevation of globotriaosylsphingosine is suggestive of Fabry disease.
Some patients with Fabry disease may have normal concentrations of globotriaosylsphingosine.
1. Alharbi FJ, Baig S, Auray-Blais C, et al: Globotriaosylsphingosine (Lyso-Gb3) as a biomarker for cardiac variant (N215S) Fabry disease. J Inherit Metab Dis. 2018 Mar;41(2):239-247. doi: 10.1007/s10545-017-0127-2
2. Vardarli I, Rischpler C, Herrmann K, Weidemann F: Diagnosis and screening of patients with Fabry disease. Ther Clin Risk Manag. 2020 Jun 22;16:551-558. doi: 10.2147/TCRM.S247814
3. Mehta A, Hughes DA: Fabry disease. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2002. Updated January 5, 2017. Accessed November 10, 2020. Available at www.ncbi.nlm.nih.gov/books/NBK1292/
Whole blood is spotted onto filter paper and dried overnight. A 3-mm dried blood spot is extracted with internal standard. The extract is subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS/MS is operated in the multiple reaction monitoring positive mode to follow the precursor to product species transitions for each analyte and internal standard. The ratio of the extracted peak areas to internal standard is determined by LC-MS/MS is used to calculate the concentration of in the sample.(Unpublished Mayo method)
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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.
82542
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
LGBWB | Globotriaosylsphingosine, B | 92753-3 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
BA4371 | Interpretation (LGBWB) | 59462-2 |
BA4370 | Globotriaosylsphingosine | 92753-3 |
BA4372 | Reviewed By | 18771-6 |