Purine Metabolism and Dystonia: Perspectives of a Long-Promised Relationship

Abstract

Dystonia research focuses on the identification of converging biological pathways, allowing to define molecular drivers that serve as treatment targets. We summarize evidence supporting the concept that aberrations in purine metabolism intersect with dystonia pathogenesis. The recent discovery of IMPDH2-related dystonia introduced a gain-of-function paradigm in purinergic system defects, offering new perspectives to understand purine-pool imbalances in brain diseases. We discuss commonalities between known dystonia-linked mechanisms and mechanisms emerging from studies of purine metabolism disorders including Lesch–Nyhan disease. Together, we hypothesize that a greater appreciation of the relevance of purine perturbances in dystonia can offer fresh avenues for therapeutic intervention. ANN NEUROL 2025;97:809–825.