A comparison of central nervous system involvement in patients with classical Fabry disease or the later-onset subtype with the IVS4+919G>A mutation

Han-Jui Lee,Dau-Ming Niu,Sheng-Che Hung,Ting-Rong Hsu,Chia-Feng Yang,Chui-Mei Tiu,Svetlana Bizjajeva,Wen-Chung Yu,Tzu-Hung Chu

doi:10.1186/s12883-017-0810-9

Abstract

BackgroundPatients with the later-onset IVS4+919G>A (IVS4) Fabry mutation are known to have positive central nervous system involvement compared with age- and sex-matched controls. This study compares central nervous system manifestations in patients with the IVS4 mutation or classical Fabry mutations.MethodsThis was a retrospective analysis of magnetic resonance imaging (MRI) data from Taiwanese patients enrolled in the Fabry Outcome Survey (sponsored by Shire; data extracted March 2015).ResultsTwenty-five IVS4 (19 males) and 12 (four males) classical Fabry patients underwent MRI at a median (range) age of 60.7 (45.0–70.4) and 43.0 (18.0–61.4) years, respectively. All patients received agalsidase alfa enzyme replacement therapy; two (16.7%) classical Fabry patients underwent MRI before treatment start. The pulvinar sign occurred in eight (32.0%; seven males) IVS4 and six (50.0%; three males) classical Fabry patients. Infarction occurred in eight (32.0%) IVS4 and four (33.3%) classical Fabry patients. Fazekas scores of 0, 1, 2, and 3 were found for 15 (60.0%), seven (28.0%), two (8.0%), and one (4.0%) of the IVS4 patients and for six (50.0%), four (33.3%), two (16.7%), and 0 classical Fabry patients, respectively. Abnormal height bifurcation of the basilar artery was observed in 40.0% of IVS4 and 58.3% of classical Fabry patients; abnormal laterality was observed in 4.0% of IVS4 and 16.7% of classical Fabry patients. Median (range) basilar artery diameter was 2.7 (1.4–4.0) mm in IVS4 and 3.2 (2.3–4.7) mm in classical Fabry patients (P = 0.0293); vascular stenosis was noted in 8.3% of IVS4 patients but in no classical Fabry patients.ConclusionsA similar range of MRI findings was found for both IVS4 and classical Fabry patients. Notably, basilar artery diameter was larger in classical Fabry patients than IVS4 patients.

Highlights

Patients with the later-onset IVS4+919G>A (IVS4) Fabry mutation are known to have positive central nervous system involvement compared with age- and sex-matched controls
White matter lesions and infarction, increased signal intensity in the lateral pulvinar, and increased diameter and tortuosity of the basilar artery [8, 10,11,12] are some of the abnormalities that have been observed upon brain magnetic resonance imaging (MRI) in patients with Fabry disease (FD)
A total of 37 Taiwanese patients registered in Fabry Outcome Survey (FOS) had brain MRI data; of these, twice as many had the IVS4 mutation (67.6%) than classical Fabry mutations (32.4%)

Summary

Introduction

Patients with the later-onset IVS4+919G>A (IVS4) Fabry mutation are known to have positive central nervous system involvement compared with age- and sex-matched controls. Fabry disease (FD, MIM 301500) is an X-linked lysosomal disorder resulting from lysosomal α-galactosidase A deficiency, which subsequently leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body [1]. White matter lesions and infarction, increased signal intensity in the lateral pulvinar (known as the pulvinar sign), and increased diameter and tortuosity of the basilar artery [8, 10,11,12] are some of the abnormalities that have been observed upon brain magnetic resonance imaging (MRI) in patients with FD. Increased diameter of the basilar artery and presence of the pulvinar sign are reportedly useful in FD diagnosis, when found alongside other, less specific, neurological findings that are known to occur in FD [10,11,12]

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