EGL Genetics Blog

Comprehensive Genetic Testing and the Diagnosis of Fabry Disease

Posted by Antonio Shaw on Dec 24, 2015 11:00:00 AM

Fabry disease is an X-linked condition caused by a deficiency of alpha-galactosidase A enzyme activity. According to the National Institutes of Health, the condition affects an estimated 1 in 40,000 to 60,000 males, and fewer females. The diagnosis of Fabry disease has increased in importance, as treatment with enzyme replacement therapy is now available. Because this condition shares symptoms commonly associated with other disorders, it is often misdiagnosed as multiple sclerosis, lupus, rheumatoid or juvenile arthritis, rheumatic fever, or neurosis.

Fabry disease is passed down to children differently depending on whether the abnormal gene on the X-chromosome is inherited from the mother or the father.




A mother affected with Fabry disease will have a 50% chance of passing the disorder to any child she may have, regardless of the child's gender. However, a father affected with the condition will have a 100% chance of passing the disorder to all of his daughters and a 0% chance of passing it to his sons.

Testing strategy for Fabry disease varies due to the gender of the patient.  EGL offers comprehensive molecular and biochemical genetic testing which may avoid misdiagnosis of Fabry disease.

Molecular Testing

Sequence and deletion/duplication analyses of the GLA gene

Our technologies detect over 99% of sequence variants in the coding region and splice junctions. If a variant is not found through sequence analysis, we recommend follow-up through targeted CGH array, used to detect deletions and duplications.

Biochemical Testing

Measurement of Alpha-Galactosidase A in Blood

Alpha-galactosidase A enzyme activity anaylsis alone should detect all males with Fabry disease. Due to the variation of alpha-galactosidase A activity found in heterozygous (carrier) females, this testing may detect approximately 60% of heterozygous females. In order to increase the speed and detection of females with Fabry disease, we recommend combining the enzyme analysis with sequencing of the GLA gene. And yes, enzyme analysis can be performed on samples at the same time as gene sequencing.

Globotriaosylceramide (GL-3) Quantification in Urine

Individuals with Fabry disease have trouble metabolizing GL-3 causing a progressive accumulation of GL-3 in epithelial and smoth muscle cells, which can lead to the restriction and obstruction of blood supply to the kidneys, heart, and brain. The measurement of GL-3 can diagnose both males and heterozygous females who have Fabry disease, in addition to monitoring enzyme replacement therapy and disease progression.

The Fabry disease Testing Roadmap, created by Emory's Lysosomal Stoarge Disease Center in Atlanta, Georgia, and other information on testing for this condition, can be found here.

The importance of genetic testing in the proper diagnosis and treatment of Fabry disease cannot be overestimated. As the oldest genetics laboratory in the country, EGL has the experience to ensure you receive the most accurate diagnostic results for this and many other genetic disorders.  For more information on testing options for this and other neurologic disorders, download our eBook, "Genetic Testing for Neurologic Disorders: A Clinician's Guide."  





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