Efficacy of zinc treatment in 2 cases with Arg209Cys mutation in GNAO1 gene

Objectives: Mutations in GNAO1 speed up GTP uptake and inactivate GTP hydrolysis by Gαo (majorneuronal G protein), resulting inconstitutive GTP binding by the G protein. This typically results in neurodevelopmental disorders, includingin voluntary movements. Zinc ions have been identified to restore GTPase activity and sypmtoms may be improved with treatment.

Methods: The clinical follow-up and treatments of two patients with Arg209Cys mutation in the GNAO1 were evaluated.

Results: Both cases had intermittant, generalized involuntary movements which started at the age of 2 and 4, respectively. First patient was treated with carbamazepine, cannabidiol, tetrabenazine and haloperidol at different times and intervals. All drugs effectiveness was lost over time, especially with febrile infections. The patient has been followed up for five months with zinc and haloperidol. Involuntary movements diminished and speech was more comprehensible initially, however this effects decreased over time. Second patient partially benefited from cannabidiol, valproate, trihexyphenidyl, tetrabenazine. Deep brain stimulation(DBS) was applied to patient who had severe rhabdomyolysis and unstoppable, continuous choreatotic movements. With 6-month zinc treatment in addition to DBS, no significant improvement was observed in her movements.

Conclusion: Although it’s shown that zinc therapy can be effective in the GNAO1 mutation at the molecular level, the clinical efficacy has not been demonstrated.
Keywords: GNAO1 mutation, zinc, movement disorder