Journal Article

Megadolichobasilar anomaly with thrombosis in a family with Fabry's disease and a novel mutation in the α-galactosidase A gene

Ferenc Garzuly, László Maródi, Melinda Erdös, János Grubits, Zita Varga, Ellen Gelpi, Béla Rohonyi, Mária Mázló, Anikó Molnár and Herbert Budka

in Brain

Published on behalf of The Guarantors of Brain

Volume 128, issue 9, pages 2078-2083
Published in print September 2005 | ISSN: 0006-8950
Published online June 2005 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awh546
Megadolichobasilar anomaly with thrombosis in a family with Fabry's disease and a novel mutation in the α-galactosidase A gene

Show Summary Details

Preview

Fabry's disease is an X-linked lysosomal storage disorder. α-Galactosidase deficiency leads to accumulation of globotriaosylceramide mainly in endothelial and smooth muscle cells. Cerebrovascular symptoms with predominant affection of the vertebrobasilar circulation are one of the major sources of morbidity in Fabry's disease. We present a Hungarian family with Fabry's disease caused by a new mutation in the α-galactosidase A gene (GLA), and describe a variant expression of the disease. Megadolichobasilar anomaly was diagnosed in two male patients in the family who died of thrombosis. In another female patient who had suffered from disturbance of the vertebrobasilar circulation, a strongly dilated basilar artery without thrombosis was found at autopsy. Another three family members had basilar strokes and large and elongated basilar arteries on MRI. Genetic analysis disclosed a c.47T→C missense mutation resulting in L16P in the amino acid sequence of the α-galactosidase protein. This report suggests that megadolichobasilar anomaly is potentially life-threatening, and that L16P is a disease-causing mutation in patients with Fabry's disease. Early enzyme replacement therapy may prevent the development of these irreversible cerebrovascular complications.

Keywords: megadolichobasilar anomaly; basilar thrombosis; Fabry's disease; angiokeratoma corporis diffusum; GLA mutation; GLA = α-galactosidase A gene; GL-3 = globotriaosylceramide; MDBA = megadolichobasilar anomaly

Journal Article.  2984 words.  Illustrated.

Subjects: Neurology ; Neuroscience

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.