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.


OBJECTIVE
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.


METHODS
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.
Essex Centre for Neurological Sciences, Queen's Hospital, Romford RM7 0AG, United Kingdom.
Tim M
TM
Young
Emma L
EL
Blakely
Helen
H
Swalwell
Janet E
JE
Carter
Luke D
LD
Kartsounis
Dominic G
DG
O'Donovan
Douglass M
DM
Turnbull
Robert W
RW
Taylor
Rajith N
RN
de Silva
D001284:Atrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D003704:Dementia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009127:Muscle Rigidity / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009483:Neuropsychological Tests; D010649:Phenylalanine / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics*
D010649:Phenylalanine; D012343:RNA, Transfer