Influence of L-dopa on subtle motor signs in heterozygous Parkin- and PINK1 mutation carriers

Parkinsonism Relat Disord. 2017 Sep;42:95-99. doi: 10.1016/j.parkreldis.2017.07.003. Epub 2017 Jul 8.


Introduction: A latent nigrostriatal deficit and its possible clinical consequences in asymptomatic heterozygous Parkin and PINK1 mutation carriers (AMC) have been a matter of investigation in recent years. Notably, mild Parkinsonian signs in heterozygous mutation carriers can be so subtle that they may be missed if not specifically investigated.

Methods: We studied 15 heterozygous Parkin and PINK1 AMC and 18 age- and sex-matched mutation-negative controls using a standardized video, instructing the probands to perform relevant parts of the UPDRS III to investigate fine motor movements at baseline and after first-time L-Dopa administration. Additionally, available UPDRS III scores of mutation carriers from the past ten years were reviewed.

Results: AMC showed a reduced number of fine motor movements per second compared to controls at baseline (p = 0.04). L-Dopa improved motor performance numerically but non-significantly in AMC (p = 0.2301), but significantly in healthy controls (p = 6.1·10-5). Although none of the AMC reported symptoms, nine showed rigidity, bradykinesia, tremor, and postural instability when the UPDRS III was applied. Mean UPDRSIII scores significantly decreased after L-Dopa administration (p = 0.005), but did not increase over the past ten years.

Conclusions: (i) Heterozygous AMC show subtle motor abnormalities when a detailed, specialized motor examination is applied and compared to mutation-negative matched control subjects. (ii) The mild motor deficit present in a subgroup of heterozygous Parkin and PINK1 AMC appears to be non-progressive and responsive to L-dopa administration. (iii) Evaluating motor changes, their progression, and treatment response in AMC can provide valuable insights into possible early disease stages and compensatory mechanisms.

Keywords: Genetics; Heterozygous; Parkinsonism; Rating scales.

MeSH terms

  • Case-Control Studies
  • Female
  • Heterozygote
  • Humans
  • Levodopa / therapeutic use*
  • Male
  • Middle Aged
  • Movement / drug effects
  • Mutation / genetics*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics*
  • Pharmacogenomic Testing
  • Protein Kinases / genetics*
  • Statistics, Nonparametric
  • Ubiquitin-Protein Ligases / genetics*


  • Levodopa
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase