Fabry disease
Fabry disease is a rare metabolic disorder caused by the absence or deficiency of the leukocyte enzyme α-galactosidase A. This enzyme is essential for the elimination of waste products from our cells, which tend to accumulate in structures called lysosomes, whose function is precisely to eliminate cellular waste.
If the enzyme is absent, Fabry disease manifests in males as early as childhood and can cause kidney, brain, or heart damage at a young age. If the enzyme is only markedly reduced, clinical manifestations appear later, usually to a significantly lesser extent and even later in females. After age 20 in males, but especially in adulthood and even later in life, particularly in females, patients may present with hypertrophic cardiomyopathy (HCM), with progressive hypertrophy, sometimes severe, isolated or associated with varying degrees of renal or other organ failure.
It is documented that about 1-5% of patients over 40 years of age have HCM due to Fabry disease.
Diagnosis:
It is performed by measuring leukocyte α-galactosidase A activity in fresh blood. If activity is reduced or absent, it is subsequently confirmed by genetic analysis of mutations in the specific gene (GLA). In males, the diagnosis of Fabry disease is ruled out if enzyme activity values are normal or only mildly reduced. However, affected females may have normal enzyme activity values, and it is preferable to perform genetic analysis immediately. The result of this analysis must be confirmed as the cause of Fabry disease by expert geneticists.
In fact, the mere identification of a genetic mutation is not sufficient to make a diagnosis of
Fabry disease.
Leukocyte α-galactosidase A enzymatic activity and genetic analysis are performed, by appointment, in a few specialized laboratories in Italy (e.g. Meyer Hospital in Florence).
However, it is also possible to use a specific card on which a drop of blood is dried, called DBS (dried blood spot), which is sent to laboratories that perform the analysis in Italy or Europe and can be stored for up to 3 months.
Therapy:
For about 20 years, it has been possible to administer the missing enzyme intravenously, which is especially effective in the early stages of the disease. An oral therapy has also been available for several years, for use when enzyme activity is only reduced. Gene therapy is also under study.
In Italy there are numerous referral centers specialized in the diagnosis and therapy of Fabry disease.
