Fabry disease is a lysosomal storage disorder that is caused by mutations in the gene encoding a-
galactosidase A on Xq22.1. Typically hemizygous male patients exhibit classic phenotypes such as
angiokeratoma, acroparesthesias, episodic
pain "crises,"
hypohidrosis, and whorl-shaped
corneal opacities from childhood. However, during adulthood, they gradually develop
kidney failure,
heart disease, and
strokes resulting in early death between 40 to 50 years of age. However, recent studies have indicated a high prevalence of disabling clinical symptoms in heterozygous females patients. Patients having the cardiac variant of
Fabry's disease exhibit only
left ventricular hypertrophy, while patients having the renal variant exhibit only
kidney failure. Individuals affected by these variants show higher residual
enzyme activity of
alpha-galactosidase A than individuals affected by the classic form of
Fabry's disease due to missense mutations of the GLA gene. The cerebrovascular involvement in
Fabry disease is not rare in both adult hemizygotes and heterozygotes.
Infarctions caused by the occulsion of small vessels involving mostly the vertebrobasilar region in approximately two-thirds of the cases, and that is associated with the deposition glycoshingolipids including GL-3 in the walls of these vessels. In Caucasian patients, elongated, ectatic, and tortuous vertebral and basilar arteries are frequently observed on MRAs. Life-threatening megadolichobasilar anomaly with
thrombosis has been identified in a large Hungarian family in which the family members share L16P mutation. On performing MRI, an increased signal intensity was observed in the pulvinar in T1-weighted images; this is the characteristic so-called "pulvinar sign".
Enzyme replacement therapy has been approved in Japan since 2004 and 2007 for
agalsidase beta and agalsidase alpha, respectively. This treatment modestly improves the
small-fiber neuropathy,
hypohidrosis,
hypertrophic cardiomyopathy, and stabilizes the renal function in the long term for up to 54 months. However, it has not helped in decreasing the incidence of
strokes.