Fabry disease is a lysomal storage disorder resulting from deficient or absent activity of the lysosomal enzyme, α- galactosidase A, and the resultant accumulation of glycosphingolipids, mainly in the endothelium.
| Clinical Features | Fabry disease is a chronic progressive condition with symptoms of chronic neuropathic pain, heat and cold intolerance, fatigue, skin lesions, cardiomyopathy and end stage renal disease. It encompasses a spectrum of phenotypes ranging from the classic to atypical renal and cardiac forms. Age of presentation for the classic form begins in early childhood, while the renal variant presents after 25 years of age, and the cardiac variant after 40 years of age. |
| Incidence | 1:50,000 in males. The cardiac Fabry mutation (IVS4+919G>A) occurs at 1:1600 in East Asia. |
| Genetics | Mutations in GLA are known to cause Fabry disease. |
| Inheritance | X-linked recessive |
| Penetrance | 100% |
| Disease Pathogenesis | The lysosomal enzyme, α- galactosidase A breaks down glycosphingolipids. Enzymatic defect leads to progressive accumulation of globotriaosylcaramide (GL3) in the lysosomes of most organs. This abnormal storage results in the selective damage of the renal glomerular and tubular epithelial cells, the myocardial cells and valvular fibrocytes, neurons of the dorsal root ganglia and autonomic nervous system, and the cells of the vascular system. Patients with absent α- galactosidase A activity exhibit widespread systemic manifestations, whereas those with an attenuated level of enzyme activity have atypical variants of Fabry disease that may cause isolated myocardial disease. |
| Indications for Molecular Testing | Confirm or establish diagnosis Predictive testing Prenatal diagnosis |
| Test Information | GLA Gene exons and intron/exon boundaries are analyzed subsequent to Sanger sequencing. Mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations. Exonic or whole-gene deletions/duplications will not be detected. Additionally, a negative result does not rule out causal gene mutations as the promoter region and cryptic splicing mutations are not investigated. |
| Clinical Sensitivity | 100% |
| Turnaround Time | 2-4 weeks |
| CPT Codes | GLA: 81405 |
Sample and Shipping Information
| Specimen | Whole blood drawn in lavender top (EDTA) tube in a volume of 3-5cc (Adults/Children) and 3 cc (infant) |
| Shipping | Refrigerate sample until time of shipping. Ship sample at room temperature in an insulated container by overnight delivery. |
| Causes for Rejection | Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container. |
References
Laney DA, Bennett RL, Clarke V, Fox A, Hopkin RJ, Johnson J, O’Rourke E, Sims K, Walter G. Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2013 Oct;22(5):555-64.
Gal A, Hughes DA, Winchester B. Toward a consensus in the laboratory diagnostics of Fabry disease – recommendations of a European expert group. J Inherit Metab Dis. 2011;34:509–14.
Nakao S, Kodama C, Takenaka T, Tanaka A, Yasumoto Y, Yoshida A, Kanzaki T, Enriquez AL, Eng CM, Tanaka H, Tei C, Desnick RJ. Fabry disease: detection of undiagnosed hemodialysis patients and identification of a “renal variant” phenotype. Kidney Int. 2003;64:801–7
Sachdev B, Takenaka T, Teraguchi H, Tei C, Lee P, McKenna WJ, Elliott PM. Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation. 2002;105:1407–11
Resources
Fabry Support and Information Group (FSIG)
108 NE 2nd Street
Suite C
PO Box 510
Concordia MO 64020
Phone: 660-463-1355
Fax: 660-463-1356
info@fabry.org
www.fabry.org
National Fabry Disease Foundation (NFDF)
4301 Connecticut Avenue Northwest
Suite 404
Washington DC 20008-2369
Phone: 800-651-9131 (toll-free)
Fax: 800-651-9135 (toll-free)
info@fabrydisease.org
www.fabrydisease.org
Fabry Registry
Genzyme Corporation
500 Kendall Street
Cambridge MA 02142
Phone: 800-745-4447 ext. 15500
Toll-Free: 617-591-5500
Fax: 617-374-7339
fabryregistry@genzyme.com
Fabry Registry