FABRY DISEASE: CLINICAL CHARACTERISTICS, DIAGNOSIS AND MANAGEMENT

Περίληψη

Fabry disease (FD) is an X-linked, lysosomal storage disorder characterized by the decreased activity of the
lysosomal enzyme, alpha-galactosidase A (α-Gal A), related to mutations in the GLA gene (Xq21.3-q22).
Deficient enzyme activity results in the accumulation of neutral glycosphingolipids and globotriaosylceramide
(Gb3) in the plasma and cellular lysosomes of different tissues and organs throughout the body.
Multi-system manifestations, such as progressive renal failure, cardiac disease, cerebrovascular disease,
small-fiber and large-fiber peripheral neuropathy, and skin lesions, among other abnormalities complete
the phenotype of FD. Diagnosis is based on the finding of reduced α-Gal A activity in leukocytes or plasma
or the detection of Gb3 accumulation in plasma, urine or biopsy specimens, while it is confirmed by
molecular genetic testing. Regarding the disease prognosis, end-stage renal disease and life-threatening
cardiovascular or cerebrovascular complications limit the life-expectancy of untreated males and females
compared to the general population. However, disease-specific treatments are currently available, including
enzyme replacement therapy and small-molecule chaperone treatment. In adjunction to symptomatic
management, these therapeutic options have the potential to modify the disease course and halt progression.
Furthermore, other treatments such as substrate reduction therapies, mRNA-based therapies and
gene therapies are being developed and tested in clinical trials. In this era when available FD-specific treatment
options are actively expanding, increased clinical suspicion and prompt and accurate diagnosis of FD
are critical for the early initiation of individualized treatment and change in the prognosis of FD patients.