Mitochondrial disease in autism spectrum disorder patients: a cohort analysis.
BACKGROUND
Previous reports indicate an association between autism spectrum disorders (ASD) and disorders of mitochondrial oxidative phosphorylation. One study suggested that children with both diagnoses are clinically indistinguishable from children with idiopathic autism. There are, however, no detailed analyses of the clinical and laboratory findings in a large cohort of these children. Therefore, we undertook a comprehensive review of patients with ASD and a mitochondrial disorder.


RESULTS
We reviewed medical records of 25 patients with a primary diagnosis of ASD by DSM-IV-TR criteria, later determined to have enzyme- or mutation-defined mitochondrial electron transport chain (ETC) dysfunction. Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism. Twenty-one patients had histories of significant non-neurological medical problems. Nineteen patients exhibited constitutional symptoms, especially excessive fatigability. Fifteen patients had abnormal neurological findings. Unusual developmental phenotypes included marked delay in early gross motor milestones (32%) and unusual patterns of regression (40%). Levels of blood lactate, plasma alanine, and serum ALT and/or AST were increased at least once in 76%, 36%, and 52% of patients, respectively. The most common ETC disorders were deficiencies of complex I (64%) and complex III (20%). Two patients had rare mtDNA mutations of likely pathogenicity.


CONCLUSIONS
Although all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism.
Weissman
Jacqueline R
JR
Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, Ohio, United States of America.
Kelley
Richard I
RI
Bauman
Margaret L
ML
Cohen
Bruce H
BH
Murray
Katherine F
KF
Mitchell
Rebecca L
RL
Kern
Rebecca L
RL
Natowicz
Marvin R
MR
D000293:Adolescent; D001321:Autistic Disorder / Q000145:classification / Q000150:complications* / Q000175:diagnosis / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics; D003937:Diagnosis, Differential; D042967:Electron Transport Complex I / Q000172:deficiency; D014450:Electron Transport Complex III / Q000172:deficiency; D005260:Female; D006801:Humans; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications*; D009154:Mutation; D010085:Oxidative Phosphorylation; D010641:Phenotype; D055815:Young Adult
D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III