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La heterogeneidad molecular en la deficiencia de acil-CoA deshidrogenasa de cadena muy larga causa cardiomiopatía
A Mathur1, H F Sims, D Gopalakrishnan
1Departments of Pediatrics, Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis Children's Hospital, St Louis, MO, USA.
Circulation
|March 17, 1999
Resumen
Los defectos genéticos en la deshidrogenasa acil-CoA de cadena muy larga (VLCAD) causan cardiomiopatía infantil. Aunque a menudo es fatal, la deficiencia de VLCAD y los problemas cardíacos son reversibles con el tratamiento.
Área de la Ciencia:
- Genética La genética.
- Trastornos metabólicos Los trastornos metabólicos son trastornos metabólicos que se producen en el cuerpo.
- Cardiología Cardiología.
Sus antecedentes:
- La cardiomiopatía primaria (CM) está cada vez más relacionada con defectos genéticos.
- La deshidrogenasa acil-CoA de cadena muy larga (VLCAD) es esencial para la producción de energía cardíaca a través de la beta-oxidación de ácidos grasos.
Objetivo del estudio:
- Investigar el papel de las mutaciones del gen VLCAD en pacientes que presentan cardiomiopatía y características de trastornos de la oxidación de los ácidos grasos.
Principales métodos:
- ADN genómico examinado mediante análisis de varianza conformacional de cadena única.
- Se realizó la secuenciación del ADN y el análisis mutacional del gen VLCAD.
- Utilizó análisis de RNA blot y ensayos de enzimas VLCAD.
Principales resultados:
- Se identificaron 21 mutaciones genéticas distintas de VLCAD en 18 pacientes; el 80% se asoció con CM.
- La CM infantil grave (67%) y la disfunción hepática (33%) fueron presentaciones comunes.
- Las mutaciones de desplazamiento de marco o en el sitio de empalme llevaron a una reducción del ARNm VLCAD y la actividad enzimática.
Conclusiones:
- La cardiomiopatía infantil es la manifestación clínica primaria de la deficiencia de VLCAD.
- Las mutaciones del gen VLCAD son diversas.
- Tanto el trastorno metabólico como la cardiomiopatía asociados con la deficiencia de VLCAD pueden revertirse, a pesar de la alta mortalidad inicial.
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