High plasma homocysteine concentrations in cerebrovascular patients with Fabry disease

Abstract number: P0434

Gensini^* F., Fedi^* S., Brogi^* D., Buechner^* S., Giusti^* B., Sestini^* I., Martinelli^* F., Bandinelli† R., Coppo^* M., Arnetoli^* G., Abbate^* R., Borsini^* W.

†Azienda Ospedaliera Careggi, Italy ^*University of Florence, Italy;

Fabry disease is a rare X-linked recessive lysosomal storage disease secondary to deficiency of alpha-galactosidase A with resulting glycolipid accumulation, particularly globotriaosylceramide (Gb3) in numerous cell types including vascular endothelial cells. Affected patients have microvascular disease of the kidneys, heart, and brain. Cerebrovascular ischemia in Fabry disease has been largely attributed to the progressive deposition of Gb3 in vascular endothelium, giving rise to thromboembolic events. Aim of this study was to evaluate the role of prothrombotic risk factors in the clinical presentation. We evaluated conventional risk factors for cerebrovascular disease and homocysteine, vitamin B6 and B12, folic acid, lipoprotein (a) and C677T MTHFR mutation in nine Fabry patients (four homozygous and five heterozygous). 4/9 had recurrent strokes or Parkinsonism with multinfartual encephalopathy. The patients were normotensive, normocholesterolemic, nondiabetic and with normal Lp(a) values. In the four patients with cerebrovascular disease we observed hyperhomocysteinemia, low levels of folate, vitamin B6 and B12, and C677T MTHFR mutation. These results suggest that hyperhomocysteinemia may contribute to the cerebral ischemic events in Fabry patients. The decreased levels of vitamins, possibly influenced by involvement of gastrointestinal apparatus, indicate the opportunity of vitamin administration in these patients.

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