Autism Studies and Related Medical Conditions, January 2009 - TACA

Values of free and total carnitine (p < 0.001), and pyruvate (p = 0.006) were
significantly reduced while ammonia and alanine levels were considerably
elevated (p < 0.001) in our autistic subjects. The relative carnitine deficiency in
these patients, accompanied by slight elevations in lactate and significant
elevations in alanine and ammonia levels, is suggestive of mild mitochondrial
dysfunction. It is hypothesized that a mitochondrial defect may be the origin of
the carnitine deficiency in these autistic children.
Filipek, P. A., J. Juranek, et al. (2003). "Mitochondrial dysfunction in autistic patients
with 15q inverted duplication." Ann Neurol 53(6): 801-4.
Two autistic children with a chromosome 15q11-q13 inverted duplication are
presented. Both had uneventful perinatal courses, normal electroencephalogram
and magnetic resonance imaging scans, moderate motor delay, lethargy, severe
hypotonia, and modest lactic acidosis. Both had muscle mitochondrial enzyme
assays that showed a pronounced mitochondrial hyperproliferation and a partial
respiratory chain block most parsimoniously placed at the level of complex III,
suggesting candidate gene loci for autism within the critical region may affect
pathways influencing mitochondrial function.
Fillano, J. J., M. J. Goldenthal, et al. (2002). "Mitochondrial dysfunction in patients with
hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome." J Child
Neurol 17(6): 435-9.
A group of 12 children clinically presenting with hypotonia, intractable epilepsy,
autism, and developmental delay, who did not fall into previously described
categories of mitochondrial encephalomyopathy, were evaluated for
mitochondrial respiratory enzyme activity levels, mitochondrial DNA, and
mitochondrial structural abnormalities. Reduced levels in specific respiratory
activities were found solely in enzymes with subunits encoded by mitochondrial
DNA in seven of eight biopsied skeletal muscle specimens evaluated. Five cases
exhibited increased levels of large-scale mitochondrial DNA deletions, whereas
pathogenic point mutations previously described in association with
mitochondrial encephalomyopathies were not found. Mitochondrial structural
abnormalities were present in three of four patients examined. Our findings
suggest that mitochondrial dysfunction, including extensive abnormalities in
specific enzyme activities, mitochondrial structure, and mitochondrial DNA
integrity, may be present in children with a clinical constellation including
hypotonia, epileptic seizures, autism, and developmental delay. The acronym
HEADD is presented here to facilitate pursuit of mitochondrial defects in patients
with this clinical constellation after other causes have been excluded.
Gargus, J. J. and F. Imtiaz (2008). "Mitochondrial energy-deficient endophenotype in
autism." American Journal of Biochemistry and Biotechnology 4(2): 198-207.
While evidence points to a multigenic etiology of most autism, the
pathophysiology of the disorder has yet to be defined and the underlying genes
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