Determinants of cerebral radiological progression in Fabry disease

Simon Körver,Leonardo Vedolin,Marcel G W Dijkgraaf,Ivo N Van Schaik,Mirjam Langeveld,Carla E M Hollak,Maria G F Longo,Mohamed El Sayed,Marjana R Lima

doi:10.1136/jnnp-2019-322268

Abstract

Background and aimIt is unclear which patients with Fabry disease (FD) are at risk for progression of white matter lesions (WMLs) and brain infarctions and whether enzyme replacement therapy (ERT)...

Highlights

Fabry disease (FD; OMIM 301500) is a rare X-inherited lysosomal storage disorder
The aim of this study was twofold: 1) to describe white matter lesions (WMLs), basilar artery diameter (BAD) and infarction progression in FD and 2) to investigate the effect of clinical characteristics, cardiovascular risk factors and enzyme replacement therapy (ERT) on the progression of WMLs and infarctions in a large retrospective cohort study conducted at a reference centre for FD
Disease characteristics Fazekas score and infarction progression risks were not related to changes in estimated glomerular filtration rate (eGFR), changes in BAD, changes in Left ventricular mass index (LVMi), presence of Discussion In this study, a large cohort of patients with FD with a known disease phenotype was followed for a median of 7 years, providing a unique dataset of >850 brain MRIs

Summary

Introduction

Fabry disease (FD; OMIM 301500) is a rare X-inherited lysosomal storage disorder. A mutation in the GLA gene leads to a deficiency of α-galactosidase A activity (enzyme commission no. 3.2.1.22). Recommended follow-up of patients with FD includes routine brain MRIs.[3] Commonly detected cerebral manifestations of FD on structural MRIs are white matter lesions (WMLs),[4] (lacunar) infarctions[5] and an increased basilar artery diameter (BAD).[6] WMLs and silent infarctions have been related to cognitive decline, clinical stroke risk and early death in the general population.[7 8] The consequences of WMLs and brain infarctions are less clear in FD, but there are indications that WMLs are related to cognitive impairment and clinical stroke.[4 9] It is unclear which patients with Fabry disease (FD) are at risk for progression of white matter lesions (WMLs) and brain infarctions and whether enzyme replacement therapy (ERT) changes this risk. Additional effects of established cardiovascular risk factors, organ involvement and treatment with ERT are probably small to negligible

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Conclusion