Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutamate carrier SLC25A12 gene.

Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2781 Oeiras, Portugal.
Journal of Autism and Developmental Disorders (Impact Factor: 3.34). 12/2006; 36(8):1137-40. DOI: 10.1007/s10803-006-0138-6
Source: PubMed

ABSTRACT In the present study we confirm 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. We further examine the involvement of the mitochondrial aspartate/glutamate carrier gene (SLC25A12) in mitochondrial dysfunction associated with autism. We found no evidence of association of the SLC25A12 gene with lactate and lactate/pyruvate distributions or with autism in 241 nuclear families with one affected individual. We conclude that while mitochondrial dysfunction may be one of the most common medical conditions associated with autism, variation at the SLC25A12 gene does not explain the high frequency of mitochondrial dysfunction markers and is not associated with autism in this sample of autistic patients.

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    ABSTRACT: IMPORTANCE Impaired mitochondrial function impacts many biological processes that depend heavily on energy and metabolism and can lead to a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). Although evidence that mitochondrial dysfunction is a biological subtype of ASD has grown in recent years, no study, to our knowledge, has demonstrated evidence of mitochondrial dysfunction in brain tissue in vivo in a large, well-defined sample of individuals with ASD. OBJECTIVES To assess brain lactate in individuals with ASD and typically developing controls using high-resolution, multiplanar spectroscopic imaging; to map the distribution of lactate in the brains of individuals with ASD; and to assess correlations of elevated brain lactate with age, autism subtype, and intellectual ability. DESIGN, SETTING, AND PARTICIPANTS Case-control study at Columbia University Medical Center and New York State Psychiatric Institute involving 75 children and adults with ASD and 96 age- and sex-matched, typically developing controls. MAIN OUTCOMES AND MEASURES Lactate doublets (present or absent) on brain magnetic resonance spectroscopic imaging. RESULTS Lactate doublets were present at a significantly higher rate in participants with ASD (13%) than controls (1%) (P = .001). In the ASD group, the presence of lactate doublets correlated significantly with age (P = .004) and was detected more often in adults (20%) than in children (6%), though it did not correlate with sex, ASD subtype, intellectual ability, or the Autism Diagnostic Observation Schedule total score or subscores. In those with ASD, lactate was detected most frequently within the cingulate gyrus but it was also present in the subcortical gray matter nuclei, corpus callosum, superior temporal gyrus, and pre- and postcentral gyri. CONCLUSIONS AND RELEVANCE In vivo brain findings provide evidence for a possible neurobiological subtype of mitochondrial dysfunction in ASD.
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