Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation

We report a family with a heterogeneous group of neurologic disorders assoc iated with the mitochondrial DNA G8363A transfer ribonucleic acid (RNA)(Lys ) mutation. The phenotype of one child in the family was consistent with au tism. During his second year of life, he lost previously acquired language skills and developed marked hyperactivity with toe-walking, abnormal recipr ocal social interaction, stereotyped mannerisms, restricted interests, self -injurious behavior, and seizures. Brain magnetic resonance imaging (MRI) a nd repeated serum lactate studies were normal. His older sister developed s igns of Leigh syndrome with progressive ataxia, myoclonus, seizures, and co gnitive regression. Her laboratory studies revealed increased MRI T-2-weigh ted signal in the putamen and posterior medulla, elevated lactate in serum and cerebrospinal fluid, and absence of cytochrome c oxidase staining in mu scle histochemistry. Molecular analysis in her revealed the G8363A mutation of the mitochondrial transfer RNA(Lys) gene in blood (82% mutant mitochond rial DNA) and muscle (86%). The proportions of mutant mitochondrial DNA fro m her brother with autism were lower (blood 60%, muscle 61%). It is Likely that the origin of his autism phenotype is the pathogenic G8363A mitochondr ial DNA mutation. This observation suggests that certain mitochondrial poin t mutations could be the basis for autism in some individuals.