Parkinsonism in GTP cyclohydrolase 1 mutation carriers

Sir,We read with great interest the article by Mencacci and colleagues (2014) reporting a significantly higher frequency of GTP cyclohydrolase 1 ( GCH1 ) variants in patients with Parkinson’s disease compared to controls. Whole-exome sequencing of a large case-control cohort showed that rare GCH1 coding variants are associated with a 7-fold increased risk of Parkinson’s disease.Heterozygous loss-of-function mutations in GCH1 , a crucial enzyme for dopamine production in nigrostriatal neurons (Kaufman, 1959; Nagatsu et al. , 1964), are the most common cause of DOPA-responsive dystonia (DRD) (Ichinose et al. , 1994). DRD is a rare hereditary disease characterized by childhood-onset, generalized dystonia and a dramatic long-lasting response to levodopa (Segawa et al. , 1976). The disease may also manifest in adulthood with parkinsonism as the sole or dominant clinical feature (Hjermind et al. , 2006; Momma et al. , 2009). GCH1 mutations have been shown to segregate in pedigrees with multiple individuals affected by isolated parkinsonism, a phenotype …