Fabry disease screening in young patients with acute ischemic stroke in Korea

Abstract

Background: Fabry disease is an X-linked lysosomal storage disorder that results from a mutation in the α-galactosidase A (GLA) gene. It shows multiple organ involvement, including cerebrovascular disease. Since Fabry disease has a prevalence of approximately 4% in young patients with cryptogenic stroke, screening for this condition is recommended for young stroke patients. This study aimed to investigate the prevalence of Fabry disease in young acute ischemic stroke patients in Korea, the distribution of GLA gene mutations, and the subtypes of ischemic stroke. Methods: This study included 211 young patients with acute ischemic stroke or transient ischemic attack. To screen for Fabry disease, α-galactosidase A (α-Gal A) enzyme activity was measured and DNA sequencing analysis of the GLA gene was performed. Results: None of the patients exhibited low α-Gal A enzyme activity or had a pathogenic GLA mutation, but 18 nonpathogenic GLA gene variants were detected, including c.-10C>T in 16 patients, c.-33C>T in one patient, and c.196G>C in one patient. The mean α-Gal A enzyme activity in 14 male patients with the c.-10C>T variant was 5.17±1.19, which was significantly lower than that of male patients with the normal genotype (7.47±3.48, P<0.05). The distribution of stroke subtypes in patients with GLA gene polymorphisms was not significantly different from that in patients with a normal genotype.Conclusions: This study demonstrates that Fabry disease is rare in young patients with ischemic stroke or transient ischemic attack in Korea, and we suggest that routine screening for Fabry disease may not be necessary for ischemic stroke patients.