J Mov Disord.  2021 May;14(2):157-160. 10.14802/jmd.20159.

Dystonia Responsive to Dopamine: POLG Mutations Should Be Considered If Sensory Neuropathy Is Present

• Qiu J
• Kumar KR
• Watson E
• Ahmad K
• Sue CM
• Hayes MW

• KMID: 2516390
• DOI: http://doi.org/10.14802/jmd.20159

Abstract

The POLG gene encodes mitochondrial DNA polymerase, and mutations in this gene cause a spectrum of disorders related to mitochondrial DNA depletion or deletion. Dystonia has only rarely been reported as an early and prominent manifestation of POLG mutations. We report a case of a 30-year-old male presenting with lower limb dystonia with peripheral neuropathy and demonstrate that the dystonia was levodopa responsive (with video findings). Whole-genome sequencing revealed biallelic variants in the POLG gene: a known pathogenic variant [NM_001126131.2:c.2209G>C (p.Gly737Arg)] and a novel likely pathogenic variant [NM_001126131.2:c.3305A>C (p.Gln1102Pro)]. A genetic diagnosis was made before the appearance of more readily recognizable features of mitochondrial disease, allowing us to avoid invasive tissue biopsies or potentially deleterious treatments, such as sodium valproate. A POLG-related disorder should be suspected in cases of dystonia with peripheral neuropathy, and this diagnosis may have implications for further investigations and management.

Keyword

Dystonia; Genetics; Peripheral Neuropathies; Parkinsonism; POLG