Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke.
ABSTRACT 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.
- Circulation Cardiovascular Genetics 06/2014; 7(3):383-92. · 5.34 Impact Factor
Article: Fabry’s disease[Show abstract] [Hide abstract]
ABSTRACT: Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the GLA gene, which leads to a deficiency in α-galactosidase A. The abnormal accumulation of glycosphingolipids, primarily globotriaosylceramide, manifests as serious and progressive impairment of renal and cardiac function. In addition, patients experience pain, gastrointestinal disturbance, transient ischemic attacks and strokes. Disease presentation in female heterozygotes may be as severe as in males although women may also remain asymptomatic. This review covers all basic aspects of the disease such as epidemiology, pathophysiology, clinical presentation by systems, diagnosis, management, prevention, and repercussions on quality of life. With the development of enzyme replacement therapy in the past few years, early initiation of treatment was found to be key for reduction of disease burden in major affected organs with improvement in neuropathic pain, decreased cardiac mass and stabilization of renal function, gastrointestinal symptoms, and hearing. This review aims to raise the awareness of the signs and symptoms of Fabry disease as well as to provide guidelines for the diagnosis and treatment.Journal of the Neurological Sciences. 01/2014;
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ABSTRACT: Provide the basis for clinical pathogeny diagnosis and discuss effective ways of curing the youth cerebral infarction in different TOAST classifications through analysis of the correlation between the youth infarction in different TOAST classifications and high homocysteine (Hcy). The selected young patients who diagnosed with cerebral infarction and admitted to the hospital in the past 3 years were regarded as the study group, and the other 136 persons picked accepted health examination in our hospital in the corresponding period were regarded as the control group, then the 136 patients were grouped according to TOAST classification; Hcy levels were determined by enzymatic cycling to compare and analyze, and NIHSS scale is applied to score. Compared with the control group, serum Hcy levels in young patients with cerebral infarction were significantly higher (P < 0.05). The statistical significance in comparative difference was found in the serum Hcy level and NIHSS score of large artery atherosclerotic (LAA) subtype from TOAST classification and the other four subtypes (P < 0.05), but such significance was absent among the other four subtypes (SAA, CA, SOE, SUE). In conclusion, the cerebral etiology of high Hcy is often related to the atherosclerosis and tends to be more serious than the other subtypes after onset of LAA, which requires more clinical attention. Early intervention and therapy are highly necessary specific to cause of disease.Cell Biochemistry and Biophysics 08/2014; 71(1). · 2.38 Impact Factor