[LS4-1D-2 ] Fabry disease in Taiwan; experience with a highly prevalent mutation
Fabry disease (FD) is an X-linked lysosomal storage disease results from mutation in the α-Galactosidase A gene that causes deficient α-Galactosidase A. The FD has two major phenotypes: type 1 classic FD and type 2 later-onset FD. The prevalence of later-onset type is much higher than the classical type. Affected males with the type 1 FD have little or no α-Gal A and have onset of acroparesthesias, hypohidrosis, angiokeratomas, and/or a characteristic corneal dystrophy in childhood or adolescence. Males with type 2 FD have residual enzyme activity, little or no vascular endothelial Gb3 accumulation, and lack of the early clinical manifestations of patients with the type 1 classic phenotype. As the age, affected type 2 males with FD develop progressive multi-systemic involvement leading to renal failure, hypertrophic cardiomyopathy, and/or cerebrovascular disease.
In Taiwan, the specific Fabry mutation, IVS4+919G>A (IVS4), has a very high prevalence about 1 in 1600 in male. With the large-scale newborn screening, a total of 1,439 individuals carrying Fabry mutations have been found and 1,201 (83.5%) were IVS4. LVH occurred in 67% of males and 32% of females over 40 years old. Severe and irreversible cardiac fibrosis developed in 38.1% of IVS4 males and 16.7% of IVS4 females without LVH. It might be too late to start ERT after hypertrophic cardiomyopathy or significant cardiac manifestations have occurred. It is also worth noticing that it is the importance of newborn screening for early detection of the insidious but ongoing irreversible cardiac damage in the patients with later-onset FD.
In Taiwan, the specific Fabry mutation, IVS4+919G>A (IVS4), has a very high prevalence about 1 in 1600 in male. With the large-scale newborn screening, a total of 1,439 individuals carrying Fabry mutations have been found and 1,201 (83.5%) were IVS4. LVH occurred in 67% of males and 32% of females over 40 years old. Severe and irreversible cardiac fibrosis developed in 38.1% of IVS4 males and 16.7% of IVS4 females without LVH. It might be too late to start ERT after hypertrophic cardiomyopathy or significant cardiac manifestations have occurred. It is also worth noticing that it is the importance of newborn screening for early detection of the insidious but ongoing irreversible cardiac damage in the patients with later-onset FD.