Mitochondrial Dysfunction in Autistic Spectrum Disorder

A retrospective analysis reveals that 32 of 41 (78%) children with autistic spectrum disorders have defective function of oxidative-phosphorylation enzymes in their skeletal muscle. The data were presented by investigators from Medical Neurogenetics, a genetic-testing facility in Atlanta, at the annual meeting of the American Academy of Neurology on Sunday.

The lead investigator, John Shoffner, MD, told Medscape Neurology & Neurosurgery that, although patients with mitochondrial disorders commonly exhibit autistic features, it is unknown how common mitochondrial disease is in autism. The US government recently decided to award compensation to the parents of Hannah Poling, after it was concluded that a concentrated series of vaccinations aggravated an underlying mitochondrial disorder, which manifested clinically as autism.

The autistic children tested by Shoffner, aged 2-16 years, were referred because of potential indicators of mitochondrial dysfunction, such as increased lactate, pyruvate, or alanine levels. By analyzing mitochondrial-enzyme activity in biopsies of skeletal muscle, defects in representative proteins from 5 mitochondrial-enzyme complexes were found. Further investigation revealed that selected proteins involved in oxidative phosphorylation were abnormal.

Among 40 children, the mitochondrial DNA (mtDNA) sequences of 10 (25%) were found to be abnormal: 2 children demonstrated heteroplasmic mutations, and abnormalities in 8 remain under investigation. Shoffner concludes that nuclear DNA mutations are, therefore, the most likely cause of the observed mitochondrial defects.