Developmental regression and mitochondrial dysfunction in a child with autism.
Autistic spectrum disorders can be associated with mitochondrial dysfunction. We present a singleton case of developmental regression and oxidative phosphorylation disorder in a 19-month-old girl. Subtle abnormalities in the serum creatine kinase level, aspartate aminotransferase, and serum bicarbonate led us to perform a muscle biopsy, which showed type I myofiber atrophy, increased lipid content, and reduced cytochrome c oxidase activity. There were marked reductions in enzymatic activities for complex I and III. Complex IV (cytochrome c oxidase) activity was near the 5% confidence level. To determine the frequency of routine laboratory abnormalities in similar patients, we performed a retrospective study including 159 patients with autism (Diagnostic and Statistical Manual of Mental Disorders-IV and Childhood Autism Rating Scale) not previously diagnosed with metabolic disorders and 94 age-matched controls with other neurologic disorders. Aspartate aminotransferase was elevated in 38% of patients with autism compared with 15% of controls (P <.0001). The serum creatine kinase level also was abnormally elevated in 22 (47%) of 47 patients with autism. These data suggest that further metabolic evaluation is indicated in autistic patients and that defects of oxidative phosphorylation might be prevalent.
Department of Neurology and Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, USA.
Jon S
JS
Poling
Richard E
RE
Frye
John
J
Shoffner
Andrew W
AW
Zimmerman
D001219:Aspartate Aminotransferases / Q000097:blood; D001321:Autistic Disorder / Q000175:diagnosis* / Q000201:enzymology; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood; D030401:Cytochrome-c Oxidase Deficiency; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000201:enzymology; D003937:Diagnosis, Differential; D042967:Electron Transport Complex I / Q000172:deficiency; D014450:Electron Transport Complex III / Q000172:deficiency; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000201:enzymology; D018482:Muscle, Skeletal / Q000473:pathology; D009133:Muscular Atrophy / Q000175:diagnosis / Q000201:enzymology; D012043:Regression, Psychology
D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III