Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke.
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.
Wozniak
Marcella A
MA
Department of Neurology, 22 South Greene Street, Baltimore, MD 21201, USA. mwozniak@som.umaryland.edu
Kittner
Steven J
SJ
Tuhrim
Stanley
S
Cole
John W
JW
Stern
Barney
B
Dobbins
Mark
M
Grace
Marie E
ME
Nazarenko
Irina
I
Dobrovolny
Robert
R
McDade
Eric
E
Desnick
Robert J
RJ
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
D000519:alpha-Galactosidase