Fabry disease is an X-linked lysosomal storage disorder resulting from the deficient activity of the lysosomal hydrolase, alpha-galactosidase A. As a result of the enzymatic defect, there is progressive accumulation of neutral glycosphingolipids with terminal alpha-galactosyl moieties (predominantly GL-3) in visceral tissues and body fluids. The enzyme is encoded by the GLA gene which is localized to Xq22.1. Affected individuals present with vascular skin lesions (angiokeratoma), acroparesthesias, hypohydrosis, and corneal and lenticular opacities. Multiorgan involvement of the kidney, heart, and CNS is observed in affected individuals with increasing age. Heterozygous females have a broad spectrum of clinical signs and symptoms, ranging from asymptomatic to having disease involvement on par with affected males. Mildly affected patients with residual enzyme activity have also been described with disease manifestations mostly limited to the heart (cardiac variant) or kidney (renal variant). Diagnostic sequencing analysis of the GLA gene coding region is now being offered for Fabry disease patients and their at-risk relatives on a clinical basis.

Reasons for Referral:

• Confirmation of diagnosis of Fabry disease
• Identification of affected females
• Carrier testing in high-risk females
• Prenatal diagnosis in cases with a known familial mutation in the GLA gene

Testing Methodology:

PCR amplification of seven exons contained in the GLA gene coding region is performed on patient genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions using automated fluorescence dideoxy sequencing methods using capillary electrophoresis.

Sensitivity:

~99% Analytical Sensitivity

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adults: 14 cc; Child: 6 cc; Infant: 6 cc
Requisition form must accompany specimen. Prior to any genetic testing, we recommend genetic counseling and request that the subject, or their legal guardian, sign our consent form and submit it with the sample. To receive our forms and information about prenatal testing, please contact our laboratory.

Turnaround Time:

4 weeks

CPT Codes and Prices:

Index: 83904X7, 83912, 83909X14, 83898X11, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Ashley G, et al. (2001) J. Hum. Genet. 46: 192-196.
2. Shabbeer, et al. (2002) Mol. Genet. Metab. 76: 23-30.
3. Garman S, Garboczi D. (2002) Mol. Genet. Metab. 77: 3-11.
4. Lai LW, et al. (2003) Clin. Genet. 63: 476-482.

Shipping Information

Forms:

 >> Gene Sequencing Requisition
 >> Prenatal Requisition

Test Codes:

Index: 6063
Known Familial Mutation: 6136
Prenatal (Known Familial Mutation Only): 6135

Medical Genetics Laboratories
Baylor College of Medicine · Houston, TX 77030
Phone: 1-800-411-GENE · Fax: 713-798-6584
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