A comparison of central nervous system involvement in patients with classical Fabry disease or the later-onset subtype with the IVS4+919G>A mutation.
BACKGROUND
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. This study compares central nervous system manifestations in patients with the IVS4 mutation or classical Fabry mutations.


METHODS
This 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).


RESULTS
Twenty-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.


CONCLUSIONS
A 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.
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Han-Jui
HJ
Lee
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
Ting-Rong
TR
Hsu
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan. hsz829@gmail.com.|School of Medicine, National Yang-Ming University, Taipei, Taiwan. hsz829@gmail.com.|Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. hsz829@gmail.com.
Sheng-Che
http://orcid.org/0000-0001-6288-3556
SC
Hung
School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Wen-Chung
WC
Yu
School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
Tzu-Hung
TH
Chu
School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
Chia-Feng
CF
Yang
Shire, Zug, Switzerland.
Svetlana
S
Bizjajeva
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Chui-Mei
CM
Tiu
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. dmniu1111@yahoo.com.tw.|Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan. dmniu1111@yahoo.com.tw.
Dau-Ming
DM
Niu
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000795:Fabry Disease / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011994:Recombinant Proteins; D012189:Retrospective Studies; D013624:Taiwan; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics*
D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase
Agalsidase alfa; Central nervous system manifestations; Fabry Outcome Survey; Later-onset Fabry disease; Magnetic resonance imaging