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

Fabry disease (or Anderson-Fabry disease) is due to the partial or total absence of the alpha-galactosidase A enzyme activity, which is in charge of degrading globotriaosylceramide (GL-3 or GB3). Since this fatty substance cannot be eliminated, it is accumulated and causes a malfunction of those sites in which it is deposited, affecting blood vessels, heart, kidney, liver, skin, and brain tissues.

It is inherited following an X-linked pattern and therefore affects men more frequently than women (these can also be affected, although generally by a later and milder form). It is estimated that 1 in 50,000 males are affected, with a prevalence in the general population of 1 in 100,000 people.
Since Fabry disease is uncommon and causes a wide range of symptoms, it can be confused with other diseases. Therefore, patients suffering from Fabry disease can go for long periods of time without a correct diagnosis. The main cardiac condition is left ventricular hypertrophy. Many of these patients are referred to doctors with a diagnosis of hypertrophic cardiomyopathy (actually, Fabry disease being the cause in 0.5%-1% of patients with hypertrophic cardiomyopathy).

• Early diagnosis of Fabry disease is essential, since nowadays there are specific treatments available: intravenous administration of the deficitary enzyme.

• Subjects under suspicion or clinical diagnosis of Fabry disease

Children and adolescents: Acute or chronic limb pain unresponsive to the usual analgesics (acroparesthesias), recurring fever of unknown origin, intolerance to heat, cold, or exercise, chronic intestinal disorders of uncertain origin, diffuse angiokeratomas, hipohydrosis, proteinuria, growth retardation, corneal opacities (cornea verticillata).

Adults: Persistence of the above-mentioned symptoms, renal insufficiency of uncertain origin, left ventricular hypertrophy (hypertrophic cardiomyopathy), dyspnea, low tolerance to exercise, angina, thoracic pain, palpitations, arrhythmia, early cerebrovascular disease, loss of hearing, and tinnitus.

• Familial study: A search for a mutation previously identified in a proband (families of patients with Fabry disease in which a mutation has been previously identified).

Disease-causing mutations are usually “point mutations”, approximately in 70% of cases, but small or large rearrangements have been described in up to 30% of cases.

Using NGS (which allows for the detection of possible deletions), the probability of detecting a positive genetic study when the disease is well characterized clinically is close to 100%.