A Case of GCH-1 Mutation Dopa-Responsive Dystonia Requiring High Doses of Levodopa for Treatment

Abstract

Background: Mutations in the GCH-1 gene are associated with Autosomal Dominant Dopamine Responsive Dystonia (DYT 5). One of the hallmarks of this condition is dramatic and sustained response to low doses of levodopa. Case Report: We present the case of a 22 year old female patient with genetically confirmed GCH-1 Dopa-Responsive Dystonia who had no response to low dose Levodopa but who achieved symptom control on a total dose of 900 mg/day. Discussion: Autosomal Dominant Dopa-Responsive Dystonia is a phenotypical heterogenous condition that, in some cases, may require high doses of levodopa for treatment response. Highlights Mutations in the GCH-1 gene are associated with Autosomal Dominant Dopamine Responsive Dystonia which is typically defined by dramatic responses to low doses of levodopa. We report a patient with genetically confirmed Dopa-Responsive Dystonia who had no response to low dose Levodopa but who achieved symptom control with 900 mg/day.

GTP cyclohydrolase 1and axanthism in ball pythons: a new vertebrate model for pterin-based pigmentation

“…GTP cyclohydrolase is a crucial cofactor in the metabolism of amino acids tyrosine, phenylalanine, and tryptophan, as well as the synthesis of neurotransmitters dopamine and serotonin (Nagatsu and Ichinose 1996; Kapatos et al 1999; Kapatos 2013). Mutations associated with BH4 deficiencies have been linked to severe metabolic and neurologic disorders (Nagatsu Ichinose 1996; Longo 2009; Fanet et al 2021), like phenylketonuria (Trujillano et al 2017), hyperphenylalaninemia (Himmelreich et al 2021), DOPA-responsive dystonia (Hirano and Ueno 1999; Klein 2014; Yoshino et al 2018; Kostić et al 2020; Bradley et al 2021), Parkinson’s disease (Mencacci et al 2014), and hereditary spastic paraplegia (Varghaei et al 2021). Indeed, GCH1 was discovered because of its association with phenylketonuria (Kaufman 1963).…”