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, Aniko Molnár, Herbert Budka

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Abstract

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.

Original languageEnglish
Pages (from-to)2078-2083
Number of pages6
JournalBrain
Volume128
Issue number9
DOIs
Publication statusPublished - Sep 2005

Keywords

  • Angiokeratoma corporis diffusum
  • Basilar thrombosis
  • Fabry's disease
  • GLA mutation
  • Megadolichobasilar anomaly

ASJC Scopus subject areas

  • Clinical Neurology

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    Garzuly, F., Maródi, L., Erdös, M., Grubits, J., Varga, Z., Gelpi, E., Rohonyi, B., Mázló, M., Molnár, A., & Budka, H. (2005). Megadolichobasilar anomaly with thrombosis in a family with Fabry's disease and a novel mutation in the α-galactosidase A gene. Brain, 128(9), 2078-2083. https://doi.org/10.1093/brain/awh546