Document Detail

Primary Carnitine Deficiency and Sudden Death: In vivo Evidence of Myocardial Lipid Peroxidation and Sulfonylation of Sarcoendoplasmic Reticulum Calcium ATPase 2.
MedLine Citation:
PMID:  22116472     Owner:  NLM     Status:  Publisher    
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.
M Mazzini; T Tadros; D Siwik; L Joseph; M Bristow; F Qin; R Cohen; K Monahan; M Klein; W Colucci
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-24
Journal Detail:
Title:  Cardiology     Volume:  120     ISSN:  1421-9751     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1266406     Medline TA:  Cardiology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  52-58     Citation Subset:  -    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Cardiac Electrophysiology Section and Cardiovascular Medicine Section, Boston University Medical Center, Boston, Mass., USA.
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