Affiliations: Laboratory for the Biological Basis of
Neurodevelopmental Disorders, Arkansas Children's Hospital Research Institute,
University of Arkansas Medical Sciences, Little Rock, AR, USA | The Mitochondrial and Metabolic Disease Center,
Departments of Medicine, Pediatrics, and Pathology, University of California,
San Diego School of Medicine, San Diego, CA, USA
Note: [] Correspondence: Dr. Richard E. Frye, M.D., Ph.D., Slot 512-41B,
Room R4025, 13 Children's Way, Little Rock, AR 72202, USA. Tel.: +1 501 364
4662; Fax: +1 501 364 1648; E-mail: [email protected]
Abstract: Although mitochondrial disease is usually associated with reductions
in electron transport chain complex activity, a few reports have associated
mitochondrial disease with complex overactivity. This is the first report to
associate complex IV overactivity with autistic disorder. Five patients with a
significant elevation in complex IV activity, abnormal muscle electron
microscopy and autistic disorder with developmental regression are reported.
The majority, 80%, manifested either epilepsy or subclinical epileptiform
discharges on electroencephalogram. Cerebral folate deficiency was found in the
three patients evaluated for this disorder. The majority of patients had
potentially detrimental nuclear and mitochondrial abnormalities. This series
represents a new mitochondrial syndrome characterized by autistic disorder with
complex IV overactivity. The association with cerebral folate deficiency is
important as cerebral folate deficiency is treatable with folinic acid. The
significance of an increase in complex IV function is discussed in the context
of the associated physiological disturbances reported in autism spectrum disorder.
Keywords: Autism, complex IV, mitochondrial dysfunction, mitochondrial DNA mutation, regression
