Fabry disease is an X-linked lysosomal storage disorder, a genetic disorder with a specific defect in lysosomal function. Deficiency of the enzyme a-galactosidase A leads to the accumulation of the sphingolipid globotriaosylceramide (Gb3, sometimes abbreviated as GL-3, and also known as ceramide trihexoside [CTH]) in almost all organs of the body. Accumulation of glycosphingolipids produces swelling and proliferation of endothelial cells. Therefore, patients can present with a number of signs or symptoms of variable degree, such as pain, heat intolerance, skin lesions, gastrointestinal complaints, hearing loss, ocular problems, or even cardiovascular or renal dysfunction. While males typically experience severe symptoms, women can range from being asymptomatic to having severe symptoms. This variability is thought to be due to X-inactivation patterns during embryonic development of the female. Fabry disease not only impairs patient quality of life, but also reduces life expectancy substantially in both genders.
The prevalence of Fabry disease has been previously estimated to be 1 per 40,000, but a prospective multicenter study of cryptogenic strokes from Germany suggests that the prevalence could be as high as 1.2%. Most of the patients are Caucasian, but it is also found in African Americans and those of Hispanic or Asian descent. Chromosomal analysis of the GLA gene is the most accurate method of diagnosis, and many mutations which cause the disease have been noted.
Since 2001 there are two enzyme replacement therapies on the market: agalsidase alpha and agalsidase beta to replace the deficient enzyme by means of infusion, most commonly every two weeks.
Plasma chitotriosidase in male Fabry patients: A marker for monitoring lipid-laden macrophages and their correction by enzyme replacement therapy.