Fabry disease. Sequencing of the GLA gene [1 gene]

Fabry disease (also known as Anderson-Fabry disease) is due to the partial or total lack of activity of the alpha-galactosidase A enzyme, involved in the degradation of globotriaosylceramide (GL-3 or GB3). When this fatty compound cannot be eliminated, it accumulates and leads to the malfunction of those sites where it deposits. The most commonly affected cells are located in blood vessels and in heart, kidney, liver, skin, and brain tissues. It follows an X-linked inheritance pattern; thus, men are affected at a higher frequency than women (who can still be affected, although generally later in life and with a milder form).

Since Fabry disease is uncommon and causes a wide range of symptoms, it can be confused with other diseases. Therefore, patients can go a long time without receiving a correct diagnosis. The main form of cardiac involvement is left ventricular hypertrophy. Many of these patients are referred for consultation with a hypertrophic cardiomyopathy diagnosis (in fact, Fabry disease is estimated to be the underlying cause of 0.5-1% of hypertrophic cardiomyopathy cases, constituting a phenocopy of this disease).

Early diagnosis of Fabry disease is essential, since a specific treatment is available nowadays, consisting of the intravenous administration of the deficient enzyme.

• It is estimated that 1 in 50,000 males is affected.
• Population-wide prevalence of 1/100,000 people.

Genetic testing in Fabry disease enables:

• Diagnostic confirmation, which allows for targeted treatment in this specific disease.
• A more accurate study of the patient’s relatives in order to provide carriers with an early/preclinical diagnosis, while non-carriers can safely be discharged from cardiological follow-up. This has proven to be a cost-effective strategy for this disease.
• An approach to the prognosis and expected clinical picture of each specific patient based on the type of genetic variant identified. Our scientific team has pioneered this type of genotype-phenotype correlation analysis.

Genetic testing is indicated in case of suspected or confirmed Fabry disease, according to the current recommendations. It is included in the diagnostic criteria for both genders and constitutes the first diagnostic step in the case of women.

The probability of testing positive when the disease has been well characterized from the clinical standpoint is close to 100%.