Fabry Disease via the GLA Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT Prenatal
7681 GLA$640 8140581405,81479 Add to Order

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Fabry disease (OMIM 301500) is a lysosomal storage disorder due to deficiency in the lysosomal enzyme glycohydrolase alpha-galactosidase A (α-GAL A) (Brady et al. N Engl J Med 276:1163-1167, 1967). The enzymatic deficiency results in the progressive accumulation of globotriaosylceramide and related glycosphingolipids in the vascular endothelium, causing the disease manifestations. Fabry disease is inherited as an X-linked recessive trait, and female carriers may develop the disease. It is a clinically heterogeneous disease even among affected members of the same family (Banikazemi et al. 2012).

In male patients with Fabry disease, two forms are recognized: the classic and atypical forms. The classic form is characterized by onset during the first two decades of life and features including corneal and lenticular opacities, angiokeratoma (skin lesions), acroparesthesias (excruciating pain in the extremities), and hypohidrosis (decreased ability to sweat). In the atypical form, symptoms begin later in life and include left ventricular hypertrophy, arrhythmias, or cardiomyopathy. The classical features are not present in cases with the atypical form of the disease.

In female heterozygotes, clinical manifestations are largely determined by random X-inactivation (Dobrovolny et al. J Mol Med 83:647-654, 2005). Female heterozygotes may be asymptomatic throughout a normal life span or affected with variable severity. Fabry disease occurs in diverse ethnic groups throughout the world, with an estimate incidence of 1 in 60,000 males (Meikle et al. JAMA 281:249-254, 1999). In untreated patients, death results from renal failure, heart failure, or myocardial infarction.

Genetics

Variants in the GLA gene are responsible for the α-GAL A enzyme deficiency and subsequent development of Fabry disease (Bernstein et al. J Clin Invest 83:1390-1399, 1989). More than 500 variants, distributed along the entire coding region of the gene have been detected in patients with Fabry disease. Most variants are unique to single families and include missense, nonsense, splicing, and small insertions/deletion variants. Partial or whole deletions of the GLA gene accounted for less than 0.05 % of all Fabry disease cases, and complex rearrangements have been detected in only three patients.

Testing Strategy

This test provides full coverage of all coding exons of the GLA gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing and CNV

This test detects GLA variants in nearly 100% of males with Fabry disease (Mehta and Hughes, GeneReviews, 2008). The sensitivity of this test in female heterozygotes is currently not known.

Indications for Test

Male patients with Fabry disease and potentially heterozygous females are candidates.

Gene

Official Gene Symbol OMIM ID
GLA 300644
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Fabry's Disease XL 301500

Related Tests

Name
Comprehensive Cardiology Panel
Pan Cardiomyopathy Panel

Citations

  • Atul Mehta, Derralynn A Hughes (2008). "Fabry Disease." PubMed ID: 20301469
  • Banikazemi et al. Genetics of Fabry Disease.
  • Bernstein, H. S., et.al. (1989). "Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene." J Clin Invest 83(4): 1390-9. PubMed ID: 2539398
  • Brady, R. O., et.al. (1967). "Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency." N Engl J Med 276(21): 1163-7. PubMed ID: 6023233
  • Dobrovolny, R., et.al. (2005). "Relationship between X-inactivation and clinical involvement in Fabry heterozygotes. Eleven novel mutations in the alpha-galactosidase A gene in the Czech and Slovak population." J Mol Med 83(8): 647-54. PubMed ID: 15806320
  • Meikle, P. J. et.al. (1999). "Prevalence of lysosomal storage disorders." JAMA 281(3): 249-254. PubMed ID: 9918480

Ordering/Specimens

Ordering Options

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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