Brain Advance Access originally published online on June 9, 2005
Brain 2005 128(9):2078-2083; doi:10.1093/brain/awh546
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Megadolichobasilar anomaly with thrombosis in a family with Fabry's disease and a novel mutation in the 
-galactosidase A gene
1 Department of Neurology, Markusovszky Hospital, Szombathely, 2 Department of Infectology and Pediatric Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, 3 Department of Neurology and 4 Department of Pathology, Erzsébet Hospital, Sopron, 5 Central Electron Microscopy Laboratory, Faculty of Medicine, University of Pécs, Pécs, 6 Dermatological Health Centre, Dr Batthyány-Strattmann László Hospital, Körmend, Hungary and 7 Institute of Neurology, Medical University of Vienna, Vienna, Austria
Correspondence to: Professor H. Budka, Institute of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 4J, 1097 Vienna, Austria E-mail: herbert.budka{at}kin.at
Fabry's disease is an X-linked lysosomal storage disorder. 
-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 -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 -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.
Key Words: megadolichobasilar anomaly; basilar thrombosis; Fabry's disease; angiokeratoma corporis diffusum; GLA mutation
Abbreviations:
GLA = -galactosidase A gene; GL-3 = globotriaosylceramide; MDBA = megadolichobasilar anomaly
Received February 7, 2005. Revised April 20, 2005. Accepted April 21, 2005.
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