Orthostatic Tremor, Progressive External Ophthalmoplegia, and Twinkle

Abstract

Mutant Twinkle increases dopaminergic neurodegeneration, mtDNA deletions and modulates Parkin expression.

The long-term outcome of orthostatic tremor

“…However, our findings corroborate and further extend three previous smaller reports10 19 20 that also failed to find reductions in striatal dopamine transporter tracer binding and indeed dopaminergic drugs are unhelpful for OT. Finally, despite rare reports of cerebellar ataxia associated with OT,7 8 21 22 we could not identify any in our cases. Although patients with OT might increase stance width, this could be compensatory to overcome the feeling of unsteadiness and/or fear of falling when standing 16…”

Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders

“…Mutations in C10orf12, as well as the mitochondrial replicase, POLG, are associated with mitochondrial DNA depletion and/or deletions with muscle biopsy findings typically involving multiple respiratory chain complex enzyme deficiency and immunohistochemical evidence of cytochrome oxidase (complex IV)-deficient muscle fibers (36). In individuals with myopathy related to MELAS, skeletal muscle biopsy may demonstrate the presence of ragged red fibers, indicative of mitochondrial proliferation (37). Seminal studies are additionally reviewed in (38).…”

Orthostatic Tremor: An Update on a Rare Entity

“…There is a single study that has identified a C10orf2 Twinkle mutation in a man with OT in his late sixties and progressive external ophthalmoplegia. 19 Twinkle is a nuclear-encoded human mitochondrial DNA helicase. 19 This observation raises the question of a possible role of mitochondrial dysfunction in the genesis of OT.…”