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Test Catalog

Test ID: AGAW    
Alpha-Galactosidase, Leukocytes

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

Diagnosis of Fabry disease in male patients

 

Verifying abnormal serum alpha-galactosidase results in male patients with a clinical presentation suggestive 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

Fabry disease is caused by deficient activity of the enzyme alpha-galactosidase A and results in damage to multiple organs including the kidney, heart, and brain.

 

Treatment with enzyme replacement therapy is available for individuals with Fabry disease.

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

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

Fabry disease is an X-linked lysosomal storage disorder resulting from deficient activity of the enzyme alpha-galactosidase A (alpha-Gal A) and the subsequent deposition of glycosylsphingolipids in tissues throughout the body, in particular, in the kidney, heart, and brain. Alterations within the GLA gene cause Fabry disease and more than 630 genetic alterations have been identified. Severity and onset of symptoms are dependent on the amount of residual enzyme activity. The classic form of Fabry disease occurs in male patients who have less than 1% alpha-Gal A activity. Symptoms usually appear in childhood or adolescence and can include acroparesthesias (burning pain in the extremities), gastrointestinal issues, multiple angiokeratomas, reduced or absent sweating, corneal opacity, and proteinuria. In addition, progressive renal involvement leading to end-stage renal disease (ESRD) typically occurs in adulthood, followed by cardiovascular and cerebrovascular disease. The estimated incidence varies from 1 in 3000 infants detected via newborn screening to 1 in 10,000 males diagnosed after onset of symptoms.

 

Male patients with residual alpha-Gal A activity greater than 1% may present with 1 of 3 variant forms of Fabry disease with onset of symptoms later in life: a renal variant associated with ESRD but without the pain or skin lesions; a cardiac variant typically presenting in the sixth to eighth decade with left ventricular hypertrophy, cardiomyopathy and arrhythmia, and proteinuria, but without ESRD; and a cerebrovascular variant presenting as stroke or transient ischemic attack. The variant forms of Fabry disease may be underdiagnosed.

 

Females who are carriers of Fabry disease can have clinical presentations ranging from asymptomatic to severely affected. Measurement of alpha-Gal A activity is not generally useful for identifying carriers of Fabry disease, as many of these individuals will have normal levels. Therefore, molecular genetic analysis of the GLA gene (FABRZ / Fabry Disease, Full Gene Analysis, Varies) is recommended as the most appropriate diagnostic test to detect carriers.

 

Unless irreversible damage has already occurred, treatment with enzyme replacement therapy (ERT) has led to significant clinical improvement in affected individuals. In addition, some adult patients may be candidates for an oral chaperone therapy. 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 (AGABS / Alpha-Galactosidase, Blood Spot), leukocytes this test), or serum (AGAS / Alpha-Galactosidase, Serum) can indicate a diagnosis of classic or variant Fabry disease. The biomarkers globotriaosylsphingosine (LGBWB / Globotriaosylsphingosine, Blood) and ceramide trihexosides (CTSU / Ceramide Trihexosides and Sulfatides, Random, Urine) may be elevated in patients with Fabry disease and may aid in the diagnostic evaluation of females. Molecular sequence 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.

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 =10.32 nmol/hour/mg protein

An interpretative report will be provided.

Note: Results from this assay do not reflect carrier status because of individual variation of alpha-galactosidase enzyme levels.

Interpretation Provides information to assist in interpretation of the test results

Values below the reference range are consistent with a diagnosis Fabry Disease.

 

When abnormal results are detected, a detailed interpretation is given, including an overview of the results and of their significance, a correlation to available clinical information, elements of differential diagnosis, recommendations for additional biochemical testing and in vitro, confirmatory studies (enzyme assay, molecular analysis), name and phone number of key contacts who may provide these studies, and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

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

Individuals with pseudodeficiency allelic variants can show reduced alpha-galactosidase A enzyme activity with this assay.

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

1. Desnick RJ, Ioannou YA, Eng CM: Galactosidase A deficiency: Fabry disease. In: Valle D, Beaudet AL, Vogelstein B, et al. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill. Accessed 2/14/19. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225546984&bookid=2709&Resultclick=2

2. De Schoenmakere G, Poppe B, Wuyts B, et al: Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients. Nephrol Dial Transplant. 2008;23:4044-4048

3. Mehta A, Hughes DA: Fabry disease. In: Pagon RA, Adam MP, Ardinger HH, et al. eds. GeneReviews. [Internet]. University of Washington, Seattle. Updated 2017 Jan 5. Accessed 2/11/2019. Available at www.ncbi.nlm.nih.gov/books/NBK1292/

4. 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

5. Laney DA, Peck DS, Atherton AM, et al: Fabry disease in infancy and early childhood: a systematic literature review. Genet Med. 2015;17:323-330

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