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.
Poling
Jon S
JS
Department of Neurology and Neurosurgery, Johns Hopkins Hospital, Baltimore, MD, USA.
Frye
Richard E
RE
Shoffner
John
J
Zimmerman
Andrew W
AW
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