Mitochondrial transfer RNA(Phe) mutation associated with a progressive neurodegenerative disorder characterized by psychiatric disturbance, dementia, and akinesia-rigidity.

BACKGROUND Mitochondrial diseases are characterized by wide phenotypic and genetic variability, but presentations in adults with akinetic rigidity and hyperkinetic movement disorders are rare. OBJECTIVES To describe clinically a subject with progressive neurodegeneration characterized by psychosis, dementia, and akinesia-rigidity, and to associate this phenotype with a novel mitochondrial transfer RNA(Phe) (tRNA(Phe)) (MTTF) mutation. DESIGN, SETTING, AND PATIENT Case description and detailed laboratory investigations of a 57-year-old woman at a university teaching hospital and a specialist mitochondrial diagnostic laboratory. RESULTS Histopathological findings indicated that an underlying mitochondrial abnormality was responsible for the subject's progressive neurological disorder, with mitochondrial genome sequencing revealing a novel m.586G>A MTTF mutation. CONCLUSIONS The clinical phenotypes associated with mitochondrial disorders may include akinesia-rigidity and psychosis. Our findings further broaden the spectrum of neurological disease associated with mitochondrial tRNA(Phe) mutations.