Primary carnitine deficiency and sudden death: in vivo evidence of myocardial lipid peroxidation and sulfonylation of sarcoendoplasmic reticulum calcium ATPase 2.
Cardiology
; 120(1): 52-8, 2011.
Article
en En
| MEDLINE
| ID: mdl-22116472
ABSTRACT
OBJECTIVES:
Primary carnitine deficiency is an autosomal recessive disorder caused by mutations in the SLC22A5 gene which results in impaired carnitine transport, cytosolic fatty acid accumulation and impaired beta oxidation. The disease is associated with cardiomyopathy and arrhythmias, but the mechanism is unknown. We hypothesized that carnitine deficiency results in increased myocardial oxidative stress.METHODS:
We evaluated a 22-year-old woman with primary carnitine deficiency and ventricular fibrillation, as well as her first-degree relatives.RESULTS:
Sequencing of SLC22A5 identified two deleterious mutations (A142S and R488H) and a novel mutation predicted to be a splice variant. Histology demonstrated increased myocardial lipid deposition and swollen mitochondria. Immunohistochemistry demonstrated accumulation of the reactive aldehyde 4-hydroxy-2-nonenal, indicative of increased lipid peroxidation, and sulfonylation of sarcoendoplasmic reticulum calcium ATPase 2 at cysteine 674.CONCLUSIONS:
These findings suggest that increased oxidant stress may contribute to myocardial dysfunction and arrhythmogenesis in this disorder.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Muerte Súbita Cardíaca
/
Hiperamonemia
/
Proteínas de Transporte de Catión Orgánico
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ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico
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Enfermedades Musculares
/
Mutación
/
Cardiomiopatías
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
Idioma:
En
Revista:
Cardiology
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos