RESUMEN
OBJECTIVE: To assess the prevalence of Fabry disease in young patients with cryptogenic stroke. PATIENTS AND METHODS: We retrospectively assessed the prevalence of Fabry disease in patients aged 16-60 years that were admitted to ZNA Middelheim Hospital from January 1, 2000 to December 31, 2004 for cryptogenic stroke. We screened for Fabry disease by measurement of alpha-galactosidase A and beta-glucuronidase activity on blood spot. In all patients with abnormal enzymatic activity and in all female patients with low normal values, genetic sequencing of the alpha-GAL-gene was performed. RESULTS: In a population of 103 young patients with cryptogenic stroke that met the in- and exclusion criteria, we were unable to identify any patient with Fabry disease. CONCLUSION: Based on the results of alpha-galactosidase A and beta-glucuronidase activity, genetic sequencing and the low prevalence of clinical signs and symptoms of Fabry disease in this population, we believe that the true prevalence of Fabry disease in patients with cryptogenic stroke may be less than currently accepted in literature.
Asunto(s)
Infarto Cerebral/epidemiología , Enfermedad de Fabry/epidemiología , Ataque Isquémico Transitorio/epidemiología , Adolescente , Adulto , Bélgica , Infarto Cerebral/diagnóstico , Infarto Cerebral/genética , Estudios Transversales , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/genética , Femenino , Pruebas Genéticas , Glucuronidasa/sangre , Glucuronidasa/genética , Humanos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/genética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Análisis de Secuencia de ADN , Estadística como Asunto , alfa-Galactosidasa/sangre , alfa-Galactosidasa/genéticaRESUMEN
In a female infant with dysmorphic features, severe neurological defects, and congenital blindness, a positive urinary Bratton-Marshall test led to identification of a massive excretion of 5-amino-4-imidazolecarboxamide (AICA)-riboside, the dephosphorylated counterpart of AICAR (also termed "ZMP"), an intermediate of de novo purine biosynthesis. ZMP and its di- and triphosphate accumulated in the patient's erythrocytes. Incubation of her fibroblasts with AICA-riboside led to accumulation of AICAR, not observed in control cells, suggesting impairment of the final steps of purine biosynthesis, catalyzed by the bifunctional enzyme AICAR transformylase/IMP cyclohydrolase (ATIC). AICAR transformylase was profoundly deficient, whereas the IMP cyclohydrolase level was 40% of normal. Sequencing of ATIC showed a K426R change in the transformylase region in one allele and a frameshift in the other. Recombinant protein carrying mutation K426R completely lacks AICAR transformylase activity.