title: Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke.
abstract: OBJECTIVE
  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.
  
  
  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 alpha-Gal A activity, and DNA from patients with consistently low plasma alpha-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 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%).
  
  
  CONCLUSIONS
  In this biracial population, unrecognized Fabry disease is a rare but treatable cause of initial ischemic stroke in young men.
authors.affiliation: Department of Neurology, 22 South Greene Street, Baltimore, MD 21201, USA. mwozniak@som.umaryland.edu
authors.forename: Marcella A
authors.initials: MA
authors.lastname: Wozniak
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kittner
authors.forename: Stanley
authors.initials: S
authors.lastname: Tuhrim
authors.forename: John W
authors.initials: JW
authors.lastname: Cole
authors.forename: Barney
authors.initials: B
authors.lastname: Stern
authors.forename: Mark
authors.initials: M
authors.lastname: Dobbins
authors.forename: Marie E
authors.initials: ME
authors.lastname: Grace
authors.forename: Irina
authors.initials: I
authors.lastname: Nazarenko
authors.forename: Robert
authors.initials: R
authors.lastname: Dobrovolny
authors.forename: Eric
authors.initials: E
authors.lastname: McDade
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D015142:Baltimore / Q000453:epidemiology; D002545:Brain Ischemia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D000795:Fabry Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D014861:Washington / Q000453:epidemiology; D044465:White People / Q000235:genetics; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics
chemical_list: D000519:alpha-Galactosidase