Frequency of unrecognized fabry disease among young european-american and african-american men with first ischemic stroke

Marcella A. Wozniak, Steven J. Kittner, Stanley Tuhrim, John W. Cole, Barney Stern, Mark Dobbins, Marie E. Grace, Irina Nazarenko, Robert Dobrovolny, Eric McDade, Robert J. Desnick

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


BACKGROUND AND PURPOSE-: The cause of initial ischemic stroke in up to 30% of young patients remains unclear. Fabry disease, due to deficient α-galactosidase A (α-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 α-Gal A deficiency is a rare cause of initial early-onset ischemic stroke in men. METHODS-: 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 α-Gal A activity, and DNA from patients with consistently low plasma α-Gal A activities were sequenced. RESULTS-: 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 α-Gal A activities, DNA sequencing identified alterations in the α-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%). CONCLUSIONS-: In this biracial population, unrecognized Fabry disease is a rare but treatable cause of initial ischemic stroke in young men.

Original languageEnglish
Pages (from-to)78-81
Number of pages4
Issue number1
StatePublished - Jan 2010


  • Brain infarction
  • Fabry disease
  • Genetic diseases
  • Genetic screening
  • Stroke
  • X-linked


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