Fabry Disease

Gene Tested: GLA Indications: • Confirmation of diagnosis in a symptomatic individual Also Known As: • Presymptomatic testing of at-risk relatives • Alpha-Galactosidase A Deficiency (GLA Deficiency) • Carrier identification in individuals with a family • Anderson-Fabry Disease history of Fabry disease • Prenatal diagnosis of an at-risk fetus, after confirmation Disorder: Fabry disease is a lysosomal storage of mutation in the mother or sibling (by prior disease caused by decreased activity of alpha-galactosidase arrangement only) A. Fabry disease is inherited as an X-linked dominant disorder and affects about 1 in 40,000 males in all ethnic Specimen: groups. Heterozygous (carrier) females may be symptomat- Blood samples should be collected in EDTA (lavender ic although the incidents of Fabry disease in females is not topped) tubes. A minimum of 5 mLs on adult or 3 mLs well ascertained. on child is required for analysis. Blood collected on Males typically present in childhood with hand pain, Friday may be stored in refrigerator until Monday for temperature intolerance, and unexplained high . overnight shipment. Around puberty, males may develop flat or slightly For other tissue requirements please call 1-800-344-2462, raised vascular lesions, abdominal pain, nausea, diarrhea, extension 4474. and absence of sweating or diminished sweating. Life threatening complications of failure, disease, Testing Methodology: PCR-based and strokes may present as early as the third to fourth sequencing of all seven exons and exon/intron boundaries decade. Without any medical intervention, males with of the GLA gene. Fabry disease typically die in their mid forties. Modern Test Sensitivity: medical interventions, such as kidney transplant and PCR-based sequencing of the GLA gene identifies a replacement therapy, may extend the lives of mutation in >99% of male patients with Fabry disease. affected males. Heterozygous females may be completely The sensitivity of DNA sequencing is over 99% for the asymptomatic or as severely affected as males. The majority detection of nucleotide base changes, as well as small of heterozygous women have a combination of signs and deletions and insertions in the regions analyzed. Multiple symptoms that present later than those in affected males. exon deletions and insertions may not be identified by this However, women remain at increased risk for kidney methodology but are rare in Fabry disease. GLA is the only failure, heart disease, and early strokes. gene associated with Fabry disease. In males, the diagnosis of Fabry disease is confirmed by measuring decreased GLA enzyme activity in plasma, Turn-Around Time: Reports are routinely leukocytes or cultured skin fibroblasts. Enzyme testing available within 21 days of sample receipt. Abnormal is unreliable in females. Molecular determination of the results will be called to the referring physician. All reports specificGLA mutation is recommended in all patients and will be faxed to the referring physician. is essential for accurate carrier testing in at-risk females.

Molecular Genetics Laboratory CLIA#: 36D0656333 Phone: (513) 636-4474 Fax: (513) 636-4373 Email: [email protected] www.cincinnatichildrens.org/molecular-genetics CPT Codes: Shipping Instructions: • GLA Full Gene Sequencing 81405 Please enclose test requisition with sample. • Family Mutation Studies 81403 All information must be completed before sample Please call 1-866-450-4198 for pricing, insurance can be processed. preauthorization, or with any billing questions. Place samples in styrofoam mailer and ship at room temperature by overnight Federal Express to arrive Results: Each test report includes a detailed Monday through Friday interpretation of the genetic findings, the clinical significance of the result, and specific recommendations Ship to: for clinical management and additional testing, if Cytogenetics and Molecular Genetics Laboratories warranted. Results will be reported to the referring 3333 Burnet Avenue NRB 1042 physician or health care provider as specified on the test Cincinnati, OH 45229 requisition form. 513-636-4474 Additional information and test requisitions are available at: www.cchmc.org/molecular-genetics

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