ArticlesPrevalence of Fabry disease in patients with cryptogenic stroke: a prospective study
Introduction
In Fabry disease, globotriaosylceramide accumulates within the vascular epithelium, kidneys, cornea, heart, and other tissues, causing renal failure, painful acroparaesthesias, typical angiokeratoma, hypohydrosis, and cardiac failure.1 The disease usually causes death in adult life from renal, cardiac, or cerebrovascular complications of vascular disease. The incidence of stroke together with vessel ectasia is about 40% in hemizygous male individuals; young people seem to be most affected. Although stroke is generally regarded as a disease of elderly people, its importance is not negligible in younger adults, and even in children. The worldwide incidence of stroke in young adults (aged 16–55 years) is estimated to be nine to 14 per 100 000 people.2 About 27% of ischaemic strokes are judged to be cryptogenic (ie, no specific cause can be identified), and cryptogenic stroke is more common in young rather than old patients.3 We aimed to measure the frequency of Fabry disease in a cohort of more than 700 young white adults aged 18 to 55 years with acute stroke.
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Patients
From February, 2001, to December, 2004, we enrolled 721 consecutive unrelated patients (432 male [60%], 289 female [40%]) from 27 different clinical departments in Germany. All patients were between 18 and 55 years of age and had had an apparently unexplained acute cerebrovascular event, a so-called cryptogenic stroke. Only those patients without typical risk factors for stroke, such as relevant nicotine abuse, significant carotid stenosis, severe obesity, cardiac emboli, patent foramen ovale,
Results
The table shows baseline clinical data for the whole cohort and for those with α-GAL mutations. A total of 32 patients (22 male, ten female) had reduced α-GAL activity and/or in the case of the women had DHPLC-screening abnormalities. DNA from these patients was sequenced for the entire coding region of the α-GAL gene. Biologically significant mutations within the α-GAL gene, which prove the diagnosis of Fabry disease, were identified in 28 patients (21 male, seven female; 4·9% and 2·4% of male
Discussion
The most important result of the study is the high frequency of Fabry disease (4%, 28/721) in this cohort of stroke patients with cryptogenic stroke aged between 18 and 55 years. On the basis that about 27% of all strokes in this age-group are of unknown cause,3 this proportion might correspond to about 1·2% in the general population of stroke patients aged between 18 and 55 years. Fabry disease must be considered in all cases of unexplained stroke in young patients, especially in cases with
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