Abstract | OBJECTIVE: To elucidate the pathophysiology of SCAD deficient patients who have a unique neurological phenotype, among fatty acid oxidation disorders, with early developmental delay, CNS malformations, intractable seizures, myopathy and clinical signs suggesting oxidative stress. METHODS: RESULTS: The most significant risk factor for vulnerability to menadione-induced oxidative stress was the presence of a FAO defect. SCADD fibroblasts were the most vulnerable compared to other FAO disorders and controls, and were similarly affected, independent of genotype. Cell death was exacerbated by hyperthermia and/or hypoglycemia. Hyperthermia was a more significant independent risk factor than hypoglycemia. Rescue significantly prolonged survival. Incubation with antioxidants and Bezafibrate significantly increased viability of SCADD fibroblasts. INTERPRETATION: Vulnerability to oxidative stress likely contributes to neurotoxicity of SCADD regardless of ACADS genotype and is significantly exacerbated by hyperthermia. We recommend rigorous temperature control in SCADD patients during acute illness. Antioxidants and Bezafibrate may also prove instrumental in their management.
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Authors | Zarazuela Zolkipli, Christina B Pedersen, Anne-Marie Lamhonwah, Niels Gregersen, Ingrid Tein |
Journal | PloS one
(PLoS One)
Vol. 6
Issue 4
Pg. e17534
(Apr 01 2011)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21483766
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antioxidants
- Vitamin K 3
- Acyl-CoA Dehydrogenase
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Topics |
- Acyl-CoA Dehydrogenase
(deficiency, metabolism)
- Adolescent
- Antioxidants
(pharmacology)
- Fibroblasts
(drug effects, metabolism, pathology)
- Humans
- Lipid Metabolism, Inborn Errors
(metabolism, pathology, physiopathology)
- Mitochondria
(drug effects, metabolism)
- Oxidative Stress
(drug effects)
- Vitamin K 3
(toxicity)
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