Fabry Disease Test Details
Fabry disease is a lysosomal storage disorder caused by deficiency of the enzyme, alpha-galactosidase A (GLA). GLA is responsible for breaking down fatty substances in the body, called globotriaosylceramides (GL-3). Deficiency of GLA results in the gradual accumulation of GL-3 in the walls of the blood vessels and tissues, such as the heart, kidneys, and brain, which causes progressive damage and potentially life-threatening problems. The spectrum of physical manifestations in Fabry disease ranges from the severe classic form to renal variants, associated with end-stage renal disease, but without characteristic skin lesions and pain crises, to milder cardiac variants. Affected males with classic Fabry disease typically have less than 1% GLA enzyme activity.Read More...
Later-onset forms of Fabry disease primarily affect the renal and/or cardiovascular systems. Individuals, typically males, with residual GLA activity (greater than 1%, more often 5–15%) may not present with classic Fabry disease, but with only a cardiac phenotype. This cardiac phenotype is characterized by hypertrophy of the left ventricle and interventricular septum, mitral valve insufficiency, and/or conduction abnormalities, which is consistent with cardiomyopathy developing in the sixth to eighth decade of life. These individuals are usually diagnosed as having "late-onset" hypertrophic cardiomyopathy (HCM).
Fabry disease is inherited in an X-linked manner, where males are more often affected than females. However, females carrying the altered gene may have physical findings, ranging from asymptomatic to severe. Enzyme replacement therapy for Fabry disease is clinically available, and early treatment may reduce the occurrence and severity of major cardiac, renal, and cerebral sequelae.
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GLA Gene Sequencing should be ordered for individuals with a clear or suspected diagnosis of Fabry disease.
This test is performed by Sanger sequencing of the coding regions and splice sites of the listed genes. This test does not detect large deletions or variants in non-coding regions that could affect gene expression.
Analytical and Clinical Sensitivity
This test is greater than 99.9% accurate in detecting variants in the sequence analyzed. Almost all clinically affected males have an identifiable pathogenic variant in GLA (GeneReviews).