Anderson-Fabry: a rare disease?

Anderson-Fabry (or Fabry) disease takes the name from the two dermatologists that independently described for the first time the pathology at the end of 1800. It is a multisystemic lysosomal storage disease, inherited in a X-linked manner. Fabry manifestations are slowly progressive, with variable age of onset, severity and clinical course. Usually, in the childhood or in the first period of the adolescence, the patients can manifest angiokeratomas, corneal or lenticular opacity, microalbuminuria or proteinuria and symptoms reflecting the involvement of peripheral nervous system, like episodic crises of acute pain, acroparesthesias, anhidrosis or hypohidrosis. With the age, there is a progression of the disease with a gradual deterioration of kidney function, that leads to End Stage Renal Disease (ESRD), and the onset of severe cardiovascular and cerebrovascular complications, that cause a reduction in quality of life in affected patients. Such complications, or a combination of these, can lead to the premature death of the patient within the fourth or fifth decade of life. In addition to the classic form, atypical variants of the disease were described: these variants manifest a mild and late-onset clinical phenotype, that is difficult to diagnose because of the involvement of a single organ. The 80% of Fabry patients are affected by these variants with a non-specific symptomatology that makes the diagnosis, which can be made in the adulthood after several years since the manifestation of the first symptoms, when the internal organs are irreversibly compromised, difficult. It was estimated a considerable delay in the diagnosis in about 40% of male patients and 70% of female patients. In particular, there is a time interval of 13 years for men and 17 years for women between the onset of the first symptoms and the correct diagnosis. Therefore, Fabry disease should be considered among the diagnostic hypothesis in all the subjects that present a systemic clinical course referable to the disease. The availability of recombinant enzyme replacement therapy has an important impact on clinical management of affected patients, improving the prognosis and the quality of life. The data in literature show the importance of a specific therapeutic intervention made as early as possible, before an irreversible organ involvement.