| 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 |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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. |
Affiliation:
|
Cardiac Electrophysiology Section and Cardiovascular Medicine Section, Boston University Medical Center, Boston, Mass., USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Sudden Gains in the Treatment of Obsessive-Compulsive Disorder.
Next Document: The Effect of Nurse-led Diabetes Self-management Education on Glycosylated Hemoglobin and Cardiovasc...