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Test Catalog

Test ID: LGBWB    
Globotriaosylsphingosine, Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosing and monitoring of patients with Fabry disease when a serum specimen is not available 

 

This test is not intended for newborn screening followup.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 renal disease, and cardiac and cerebrovascular disease. There are renal and cardiac variant forms of Fabry disease that may be underdiagnosed. Females 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 males diagnosed after onset of symptoms.

 

Unless irreversible damage has already occurred, treatment with enzyme replacement therapy (ERT) 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 (AGA / 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 males. Molecular genetic testing is the recommended diagnostic test for females 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 males and females.

 

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 females, individuals with novel GLA variants of unclear clinical significance, as well as asymptomatic patients identified by family screening.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Cutoff: < or =0.034 nmol/mL

Interpretation Provides information to assist in interpretation of the test results

An elevation of globotriaosylsphingosine (LGb3) is suggestive of Fabry disease.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Some patients with Fabry disease may have normal concentrations of globotriaosylsphingosine (LGb3).

Clinical Reference Recommendations for in-depth reading of a clinical nature

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/