Fabry disease presenting with lacunar stroke and cerebral white matter lesions, referred as possible demyelination

<h3></h3> Fabry disease (FD) is a rare, x-linked, lysosomal storage disorder. Galactosidase-Alpha (GLA) gene mutations, cause deficiency in alpha-galactosidase-A enzyme, leading to accumulation of GLP-3 (globotriaosylceramide) within cellular compartments, resulting in progressive cellular dysfunction. Vascular endothelial accumulation of GLP-3 increases risk of cerebrovascular disease in FD. We describe the case of a previously healthy, 50-year-old female, who presented with isolated dysarthria. MRI brain showed multiple T2/FLAIR hyperintensities in the supratentorial white matter bilaterally, which raised concerns regarding possible demyelination. There was also an acute lacunar infarct in the left gangliocapsular region. Antiplatelet, antihypertensive and statin medications were initiated. She underwent full neuroaxis MRI, CSF analysis, and visual-evoked potentials, which excluded demyelination. Work up for young stroke revealed a low normal level of alpha-galactosidase A at 9.8nmol/h/ml (8.9 – 39). Subsequent GLA gene testing identified a likely heterozygous pathogenic variant associated with FD. Young-onset stroke is a recognised clinical manifestation of FD, and can be the presenting feature. Cerebral white matter lesions are common and, when affecting periventricular and subcortical regions, can mimic demyelination. FD treatment is available, with enzyme replacement, therefore screening should be considered in those presenting with young-onset stroke or unexplained cerebral white matter lesions in keeping with microangiopathy.