[Fabry disease]

Fabry disease, also known as Anderson-Fabry disease or angiokeratoma corporis diffusum universale, is an X-linked recessive form of sphingolipidosis caused by total or partial deficiency of the lysosomal hydrolase, alpha-galactosidase A. From the youngest age, it results in a gradual ubiquitous build-up of glycosphingolipids that are not degraded by the missing enzyme. Cutaneous, neurological, nephrologic, cardiac, gastrointestinal, ophthalmological, respiratory, cochleovestibular and haematological involvement are responsible for increased mortality and significant impairment of quality of life in subjects affected by the disease. Angiokeratomas are the most common cutaneous sign of this disease, although they are not specific to it and must be distinguished from angiokeratomas either occurring in isolation or associated with systemic diseases. Other cutaneous signs encountered in this disease include hyperhidrosis, oral lesions, lower limb oedemas, etc. The diagnosis is mainly clinical and should be considered in the presence of a personal and/or familial history; it is confirmed by assay of enzyme activity within leucocytes or by molecular studies. Management is multidisciplinary and involves symptomatic treatment as well as specific treatment, resulting in improved survival and enhanced quality of life for patients presenting the disease. Enzyme replacement therapy with alpha-galactosidase A forms the cornerstone of specific treatment and may be associated with other types of treatments such as galactose and molecular chaperones. Gene therapy is now also used extensively. At present, these marked therapeutic advances, which closely involve dermatologists, could help transform the prognosis for patients presenting Fabry disease.