title: Megadolichobasilar anomaly with thrombosis in a family with Fabry's disease and a novel mutation in the alpha-galactosidase A gene.
abstract: Fabry's disease is an X-linked lysosomal storage disorder. alpha-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 alpha-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 alpha-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.
authors.affiliation: Department of Neurology, Markusovszky Hospital, Szombathely, Austria.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Garzuly
authors.forename: László
authors.initials: L
authors.lastname: Maródi
authors.forename: Melinda
authors.initials: M
authors.lastname: Erdös
authors.forename: János
authors.initials: J
authors.lastname: Grubits
authors.forename: Zita
authors.initials: Z
authors.lastname: Varga
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelpi
authors.forename: Béla
authors.initials: B
authors.lastname: Rohonyi
authors.forename: Mária
authors.initials: M
authors.lastname: Mázló
authors.forename: Anikó
authors.initials: A
authors.lastname: Molnár
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
mesh_terms: D000328:Adult; D000368:Aged; D001488:Basilar Artery / Q000002:abnormalities*; D000795:Fabry Disease / Q000201:enzymology / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D013927:Thrombosis / Q000201:enzymology / Q000235:genetics*; D000519:alpha-Galactosidase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000519:alpha-Galactosidase