The cause of initial ischemic stroke in up to 30% of young patients remains unclear. Fabry disease, due to deficient alpha-galactosidase A (alpha-Gal A) activity, is a vascular endothelial glycosphingolipid storage disease typically presenting in childhood. With advancing age, patients develop renal, cardiac, and cerebrovascular disease and die prematurely. A European study suggested an increased prevalence of unrecognized Fabry disease in patients with cryptogenic stroke. We hypothesized that alpha-Gal A deficiency is a rare cause of initial early-onset ischemic stroke in men.
The Stroke Prevention in Young Men Study enrolled >550 men (15 to 49 years) with first ischemic stroke in the Baltimore-Washington area in 2004 to 2007. Frozen plasma samples were assayed for alpha-Gal A activity, and DNA from patients with consistently low plasma alpha-Gal A activities were sequenced.
The study sample consisted of 558 men (42% African-American; median age 44 years). Stroke was cryptogenic in 154 men (40% African-American). In 10 patients with low plasma alpha-Gal A activities, DNA sequencing identified alterations in the alpha-Gal A gene in 2 patients. The polymorphism, D313Y, which results in low plasma enzyme activity, but near normal levels of cellular activity was seen in one European-American male. The Fabry disease-causing A143T mutation was seen in an African-American male with cryptogenic stroke (0.18% of all strokes: upper 95% CI=0.53%; 0.65% of cryptogenic strokes: upper 95% CI=1.92%).
In this biracial population, unrecognized Fabry disease is a rare but treatable cause of initial ischemic stroke in young men.
"In recent years, the involvement in heterozygous females has been more extensively documented [1, 5, 8, 9, 12, 43]. Heterozygotes for the classic phenotype of Fabry disease can be asymptomatic throughout life or have as severe manifestations as affected males [1, 5, 8, 9, 12, 42–44]. Most mutation-confirmed heterozygotes have the corneal opacities, which are observed by slit-lamp microscopy and are a useful diagnostic finding. "
[Show abstract][Hide abstract] ABSTRACT: Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme α-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses of results from ongoing studirs will add to the decision on whether or not to screen young stroke patients for Fabry disease. Finally, stroke prophylactic therapy should be used liberally in patients of both genders with verified Fabry disease. This includes primary prevention such as lifestyle counseling, targeting blood pressure, managing atrial fibrillation, diabetes mellitus, hyperlipidaemia, and ASA.
Stroke Research and Treatment 06/2011; 2011:615218. DOI:10.4061/2011/615218
". In a larger Belgian study including 1000 patients with stroke, unexplained white matter lesions or vertebrobasilar dolichoectasia, the same authors reported that ␣-Gal A deficiency may play a role in up to 1% of young patients although the clinical relevance was unclear in all the cases reported . In two other studies including only first ischemic stroke, Fabry disease prevalence was reported in 0.18% of 558 males of European- American and African-American origin  and in about 1% of 300 males and 1.5% of 193 females of Portuguese origin, excluding the D313Y polymorphism . Despite these studies, Fabry disease remains quite under diagnosed . "
[Show abstract][Hide abstract] ABSTRACT: Several epidemiologic studies suggest that Fabry disease should be considered in young patients with cryptogenic stroke. We report a case of a young woman presenting with recurrent ischemic strokes who was finally diagnosed with Fabry disease after impaired kidney function had been identified. Fabry disease should be considered in unexplained cases of first or recurrent strokes in young patients disregarding the gender of the patient, especially when chronic kidney disease and/or proteinuria are present. Renal function should be closely monitored in patients with strokes and followed up after the event. In this case, intravenous thrombolysis was performed after the second ischemic event. No other case of thrombolysis for ischemic stroke in Fabry disease has been described in the literature.
"Fabry disease is a progressive condition with life-threatening renal, cardiac and cerebrovascular manifestations that generally develope during the third or fourth decade of life . Wozniak et al.  collected data of hospitalized men, aged 15 to 49 years, with a first cerebral infarction identified by discharge surveillance. They described 0.65% of patients with cryptogenic strokes had previously not been diagnosed with Fabry disease. "
[Show abstract][Hide abstract] ABSTRACT: Fabry disease is an X-linked lysosomal disease caused by deficiency of α-galactosidase, in which early diagnosis may be missed due to the wide variety of clinical symptoms presenting during disease progression. A 13 year-old boy visited our pain clinic complaining of pricking and burning pain in the toe tips of both feet. Continuous epidural infusion for pain management was performed because of oral analgesics ineffectiveness. The patient underwent α-galactosidase A (GLA) enzyme analysis based on the clinical impression of Fabry disease from pain with a peripheral neuropathic component and history of anhidrosis. He was diagnosed with Fabry disease after confirming mutation of the GLA gene through a screening test of GLA activity. Enzyme replacement therapy was initiated and pain was tolerated with oral analgesics.
The Korean journal of pain 09/2010; 23(3):207-10. DOI:10.3344/kjp.2010.23.3.207
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