Evidence of Mitochondrial Dysfunction in Autism and Implications for Treatment

Abstract

Classical mitochondrial diseases occur in a subset of individuals with autism and are usually caused by genetic anomalies or mitochondrial respiratory pathway deficits. However, in many cases of autism, there is evidence of mitochondrial dysfunction (MtD) without the classic features associated with mitochondrial disease. MtD appears to be more common in autism and presents with less severe signs and symptoms. It is not associated with discernable mitochondrial pathology in muscle biopsy specimens despite objective evidence of lowered mitochondrial functioning. Exposure to environmental toxins is the likely etiology for MtD in autism. This dysfunction then contributes to a number of diagnostic symptoms and comorbidities observed in autism including: cognitive impairment, language deficits, abnormal energy metabolism, chronic gastrointestinal problems, abnormalities in fatty acid oxidation, and increased oxidative stress. MtD and oxidative stress may also explain the high male to female ratio found in autism due to increased male vulnerability to these dysfunctions. Biomarkers for mitochondrial dysfunction have been identified, but seem widely under-utilized despite available therapeutic interventions. Nutritional supplementation to decrease oxidative stress along with factors to improve reduced glutathione, as well as hyperbaric oxygen therapy (HBOT) represent supported and rationale approaches. The underlying pathophysiology and autistic symptoms of affected individuals would be expected to either improve or cease worsening once effective treatment for MtD is implemented.

Mitochondrial Dysfunction in Early Diagnosed Autism Spectrum Disorder Children

“…Inhibition of aerobic respiration leads to â-oxidation impairment and decreases cellular energy level that lead to increase in anaerobic respiration. So, lactate level increases 9 .…”

“…In mitochondrial dysfunction ATP level decreases that impairs urea cycle. So ammonia level in blood increases 9 . Increased ammonia level in autism spetrum disorder children may lead to toxicity and ATP depletion in brain 11 .…”

“…Skeletal muscle, gastrointestinal system and brain contain large numbers of mitochondria. In addition, mitochondrial dysfunction causes impairment of neuronal function, with imbalance in excitatory and inhibitory neurotransmitters 9 . The mitochondrial disorders are based on clinical, biochemical, molecular and histological findings.…”

“…Enzymes of these organs comes out of cell. So serum creatinine kinase (CK), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) rises 9 . Some researcher found increased ammomia and lactate level in a study 12 .…”

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“…It is a major component of non-specific immune response in host cells exposed to exogenous double-stranded RNA. This inturn precipitates the phosphorylation of eukaryotic initiation factor 2a (eIF2-a), a gene known to hinder viral replication, by blocking protein synthesis (6,10). Romark first showed that chronic HCV patients were cured with nita-…”