Speech and swallowing abnormalities in adults with POLG associated ataxia (POLG-A).

BACKGROUND

Mutations in the nuclear-encoded mitochondrial DNA polymerase gamma (POLG) can result in a wide spectrum of neurological deficits. A common presentation is progressive ataxia (POLG-A) which includes impaired speech and swallowing. The nature, severity and impact of these deficits in POLG-A is not known. A comprehensive quantitative and qualitative characterization of dysarthria and dysphagia in this recurrent ataxia disorder will assist in diagnostics, provide insights into the underlying pathology, and establish the foundation for future therapy trials.

METHODS

14 consecutive patients with POLG (9 females, mean age=50.1y, SD=11.2) and 34 healthy controls were enrolled. Comprehensive assessments of motor speech and swallowing function, acoustic analysis of speech, videofluoroscopy and measures of quality of life were conducted.

RESULTS

The speech profile of individuals with POLG-A was characterized by poor control of pitch and strain-strangled voice quality, reduced rate of speech and longer variable silences between words, and articulatory breakdown including imprecise consonants and vowel distortions. Swallowing deficits included slower initiation of the swallow reflex, poor control of bolus and late epiglottic closure. Speech and swallowing related quality of life was worse than healthy controls.

CONCLUSIONS

The dysarthria and dysphagia profiles in POLG-A are largely symptomatic of impaired timing, indicating a mainly spinocerebellar deficit. Dysarthria and dysphagia contribute to a significant impairment in functional quality of life, and progress distinctly from other POLG-A dysfunctions like ataxia or cognitive impairment. Our assessments establish meaningful patient focused outcome measures that will be suitable for use in natural history studies and clinical trials.