ABSTRACT
Fabry disease is the second most frequent lysosomal storage disorder. It is a X-linked genetic disease secondary to alpha-galactosidase A enzyme deficiency. This is a progressive and systemic disease that affects both males and females. Classical symptoms and organ involvements are acral pain crisis, cornea verticillata, hypertrophic cardiomyopathy, stroke and chronic kidney disease with proteinuria. Nevertheless, organ damages can be missing or pauci-symptomatic and other common symptoms are poorly recognised, such as gastrointestinal or ear involvement. In classical Fabry disease, symptoms first appear during childhood or teenage in males, but later in females. Patients may have non-classical or late-onset Fabry disease with delayed manifestations or with single-organ involvement. Recognition of Fabry disease is important because treatments are available, but it may be challenging. Diagnosis is easy in males, with dosage of alpha-galactosidase A enzyme activity into leukocytes, but more difficult in females who can express normal residual activity. Other plasmatic biomarkers, such as lyso-globotriaosylceramide (lyso-Gb3), are interesting in females, but need to be associated with GLA gene analysis. In this review, we aimed at summarize the main clinical manifestations of Fabry disease and propose a practical algorithm to know how to diagnose this complex disease.
