Fabry's disease—an important risk factor for stroke

In today's Lancet, Arndt Rolfs and colleagues describe the prevalence of Fabry's disease (MIM 301500, α-galactosidase A mutations) in a large cohort of patients with cryptogenic stroke. 1 Rolfs A Böttcher T Zschiesche M et al. Prevalence of Fabry disease in young patients with cryptogenic stroke: a prospective study. Lancet. 2005; 366: 1794-1796 Summary Full Text Full Text PDF PubMed Scopus (403) Google Scholar Fabry's disease is an under-recognised single-gene defect caused by α-galactosidase A deficiency, which results in a failure to catabolise α-D-galactosyl glycolipid moieties. Increased concentrations of glycolipid are a risk factor for cardiomyopathy, cardiac conduction abnormalities, valvular defects, coronary artery disease, renal failure, and stroke. Other abnormalities include painful small-fibre peripheral neuropathy, and diagnostically useful dermatological and ophthalmic hallmarks (figure). 6·3% of patients with late-onset idiopathic hypertrophic cardiomyopathy 2 Sachdev B Takenaka T Teraguchi H et al. Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation. 2002; 105: 1407-1411 Crossref PubMed Scopus (500) Google Scholar and 0·16–1·2% of patients in the general population undergoing chronic renal dialysis have been found to have Fabry's disease. 3 Kotanko P Kramar R Devrnja D et al. Results of a nationwide screening for Anderson-Fabry disease among dialysis patients. J Am Soc Nephrol. 2004; 15: 1323-1339 Crossref PubMed Scopus (167) Google Scholar , 4 Nakao S Kodama C Takenaka T et al. Fabry disease: detection of undiagnosed hemodialysis patients and identification of a "renal variant" phenotype. Kidney Int. 2003; 64: 801-807 Crossref PubMed Scopus (375) Google Scholar , 5 Linthorst GE Hollak CEM Korevaar JC Van Manen JG Aerts JM Boeschoten EW α-galactosidase A deficiency in Dutch patients on dialysis: a critical appraisal of screening for Fabry disease. Nephrol Dial Transplant. 2003; 18: 1581-1584 Crossref PubMed Scopus (66) Google Scholar In Rolfs' study, strokes in the Fabry's group were similar to those arising from other causes and affected both hemizygous men and heterozygous women; however, they occurred more frequently in the posterior cerebral circulation area and consisted of both large and small vessel ischaemic lesions. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective studyWe have shown a high frequency of Fabry disease in a cohort of patients with cryptogenic stroke, which corresponds to about 1·2% in young stroke patients. Fabry disease must be considered in all cases of unexplained stroke in young patients, especially in those with the combination of infarction in the vertebrobasilar artery system and proteinuria. Full-Text PDF