Test Catalog

Test ID: LGB3S    
Globotriaosylsphingosine, Serum

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

Diagnosis and monitoring of Fabry disease

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test is used to diagnose and monitor patients with Fabry disease.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

The following algorithms are available in Special Instructions:

-Fabry Disease: Newborn Screen-Positive Follow-up

-Fabry Disease Testing Algorithm

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. Heterozygous females 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 3,000 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 US states early detection of Fabry disease through newborn screening has been implemented.

 

Absent or reduced alpha-Gal A in blood spots, leukocytes (AGA / 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) allows for detection of the disease-causing mutation in males and females. Molecular genetic testing is the recommended diagnostic test for females as alpha-galactosidase activity may be in the normal range in an affected female patient. 

 

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 or globotriaosylsphingosine (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.

< or =1.0 ng/mL

Interpretation Provides information to assist in interpretation of the test results

Elevation of globotriaosylsphingosine (Lyso-GB3)is diagnostic for Fabry disease.

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

Carrier detection using globotriaosylsphingosine (Lyso-GB3)is unreliable.

 

Some patients with Fabry disease, and patients with pseudodeficiency of alpha-galactosidase enzyme, may have normal concentrations of globotriaosylsphingosine (LGb3).

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

1. Aerts JM, Groener JE, Kuiper S, et al:  Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci USA 2008;105(8)2812-2817

2. Mehta A, Hughes DA: Fabry Disease. In GeneReviews. 2002 Aug 5, Updated 2013 Oct 17. Edited by RA Pagon, MP Adam, HH Ardinger, et al: Seattle, WA. University of Washington, Seattle; 1993-2015. Accessed 6/21/17. 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;22:555-564

4. Laney DA, Peck DS, Atherton AM, et al: Fabry disease in infancy and early childhood: a systematic literature review. Genet Med 17(5) 323-330. Accessed 6/21/17. Available at www.nature.com/gim/journal/vaop/ncurrent/pdf/gim2014120a.pdf

Special Instructions Library of PDFs including pertinent information and forms related to the test