Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers: Figure 1

Sir, We read with great interest the recent article by Mencacci et al. (2014) about the increased risk for Parkinson’s disease in carriers of GCH1 mutations. GCH1 mutations are the most common cause of DOPA-responsive dystonia (DRD), a disorder characterized typically by lower limb dystonia with onset in childhood, an excellent, sustained response to levodopa, absence of levodopa-induced dyskinesias, and absence of dopaminergic neurodegeneration as evidenced by normal dopamine transporter (DAT) imaging. Inheritance of GCH1 -linked DRD is autosomal dominant and penetrance is incomplete (Charlesworth et al. , 2013). Mencacci et al. (2014) demonstrated that some GCH1 mutation carriers who did not manifest DRD during childhood, developed adult-onset parkinsonism with imaging evidence of dopaminergic neurodegeneration. Thus, the same GCH1 mutations may result in two distinct phenotypes: a non-degenerative phenotype typically consisting of childhood-onset DRD, and a neurodegenerative phenotype consisting of parkinsonism with onset in later life (Parkinson’s disease). Intriguingly, none of the reported GCH1 mutation carriers with imaging evidence of dopaminergic degeneration (Kikuchi et al. , 2004; Hjermind et al. , 2006; Eggers et al. , 2012; Ceravolo et al. , 2013; Mencacci et al. , 2014) had dystonia in childhood. Conversely, no childhood-onset DRD cases with GCH1 mutations have been reported to have abnormal nigrostriatal dopaminergic imaging in adult life (Snow et al. , 1993; Turjanski et al. , 1993; Jeon et al. , 1998; Mencacci et al. , 2014). Thus, currently available data suggest that the degenerative …