Dyskinesias as a limiting factor in the treatment of Segawa disease

Patients with autosomal dominant Segawa disease (dopa-responsive dystonia) demonstrate excellent, sustained response to low-dose levodopa. In contrast, the development of levodopa limiting treatment dyskinesias is thought to support the diagnosis of other early-onset dystonia/parkinsonism syndromes. We describe an atypical phenotype of persistent treatment limiting dyskinesias in a family with prominent brachial dystonia and a novel GCH1 mutation. The pedigree comprised two affected members: the proband (aged 13 years) and her mildly affected mother (aged 48 years). A phenylalanine loading test, cerebrospinal fluid for biogenic amines and pterins, guanosine triphosphate cyclohydrolase I enzyme activity, and direct exonic sequencing of GCH1 revealed a novel mutation (c.235_240delCTGAGC [p.L79_S80del]) in the GCH1 gene. Despite continuous levodopa therapy from age 7 years, the proband developed severe writer's cramp at age 10 years and persistent treatment limiting dyskinesias, with even low doses of levodopa leading to treatment challenges. Dyskinesias as limiting side effects of levodopa should not preclude a diagnosis of dopa-responsive dystonia during diagnostic levodopa trials. A diagnosis of Segawa disease should still be considered if partial improvement occurs with levodopa, but with dose-limiting dyskinesias.