the latest on mitochondrial dysfunction

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[iN1-1.004] Oxidative Phosphorylation (OXPHOS) Defects in Children with Autistic Spectrum Disorders Shoffner, C. Hyams, Genevieve N. Langley, Atlanta, GA OBJECTIVE: To retrospectively survey patients with autistic spectrum disorders that were evaluated clinically for mitochondrial disease and to assess the clinical and laboratory features of this group of patients. BACKGROUND: Autism is a developmental disorder characterized by disturbance in language, perception and socialization. A variety of biochemical, anatomical and neuroradiographical studies imply a disturbance of brain energy metabolism in autistic patients. Recent studies confirmed the previously reported high frequency of biochemical markers of mitochondrial dysfunction, namely hyperlactacidemia and increased lactate/pyruvate ratio, in a significant fraction of 210 autistic patients. (J Autism Dev Disord, 2006. 36:1137) Although rare, Mecp2 mutations can produce autistic features and the mouse model has significant mitochondrial defects. (Mol Cell Biol, 2006. 26: 5033) Additional genetic defects associated with mitochondrial dysfunction include inverted 15q11-13 duplication (Complex III defect) (Ann Neurol, 2003,53,801), A3243G mutation (mitochondrial transfer RNALeucine(UUR) gene, mtDNA depletion(J Pediatr, 2004,144,81), G8363A mutation (mitochondrial transfer RNALysine gene. (J Child Neurol, 2000,15,357). DESIGN/METHODS: Retrospective analysis of 37 children with autistic spectrum disorders. Clinical, biochemical, metabolic, and genetic data is assessed. RESULTS: Twenty four children (65%) had skeletal muscle OXPHOS defects: Complex I (16), Complex I and Complex III (5), Complex III (1), Complex I and Complex IV (2). Thirteen (35%) had normal skeletal muscle OXPHOS enzyme activities for Complexes I-IV. Clinical, metabolic, protein chemistry, and sequencing of coding regions of the mitochondrial DNA will be reported. CONCLUSIONS/RELEVANCE: Most children with autistic spectrum disorders do not have recognizable abnormalities on a broad range of imaging, metabolic and genetic studies. However, a subset of patients do harbor significant defects in oxidative phosphorylation function. Complex I abnormalities are the most frequently encountered defect. Recognition of these children is important for understanding how genes that produce autistic spectrum disorders impact mitochondrial function. Supported by: Horizon Molecular Medicine.Category - Neurogenetics and Gene TherapySubCategory - OtherSunday, April 13, 2008 2:45 PMPlatform Session: Integrated Neuroscience: Autism (2:00 PM-3:15 PM)Room: 187The embargo for all abstracts to be presented at the 60th Annual Meeting is in effect until the date and time of the presentation unless otherwise noted on the abstract and/or press release. If there are questions, please contact the AAN media and public relations team.**************Need a new ride? Check out the largest site for U.S. used car listings at AOL Autos.(http://autos.aol.com/used?NCID=aolcmp00300000002851)Need a new ride? Check out the largest site for U.S. used car listings at AOL Autos.