A case of dopa-responsive dystonia with a novel GCH1 variant c.579 C > G (p.Ile193Met)

Dopa-responsive dystonia (DRD) is an underdiagnosed inherited movement disorder characterized by childhood-onset progressive dystonia, diurnal symptom luctuation, and exquisite responsiveness to low-dose levodopa. Misdiagnosis as epilepsy, cerebral palsy, or juvenile Parkinsonism is common due to overlapping phenotypes and non-specific auxiliary examinations.

A 22-year-old Chinese female presented with an 18-year history of right-sided limb and perioral involuntary movements, slurred speech, and progressive hypertonia. She was misdiagnosed with epilepsy for over a decade with no response to antiepileptic therapy. Brain MRI, EEG, and routine laboratory tests were unremarkable. Whole-exome sequencing (WES) identiied a heterozygous guanosine triphosphate cyclohydrolase-1 (GCH1) variant c.579C>G (p.Ile193Met), classified as a variant of uncertain signiicance (VUS) per American College of Medical Genetics and Genomics (ACMG) guidelines. Low-dose levodopa/benserazide (Madopar 0.125 g tid) induced dramatic symptomatic improvement, with sustained remission at 6-month follow-up.

This case expands the GCH1 mutational spectrum of DRD and highlights the critical role of levodopa trial in unexplained dystonia, even in the absence of diurnal luctuation. Early recognition and intervention are pivotal for favorable prognosis.