Atypical presentation of dopa‐responsive dystonia in Taiwan

Abstract

The typical clinical presentation of dopa‐responsive dystonia, which is also called Segawa disease, is a young age of onset, with predominance in females, diurnal fluctuation of lower limb dystonia, and fair response to low‐dose levodopa. This disease has both autosomal dominant and autosomal recessive inheritance. Autosomal dominant Segawa disease is caused by GCH1 mutation on chromosome 14q22.1‐q22.2. Here, we report the case of a male patient with genetically confirmed Segawa disease and atypical presentations including no diurnal symptom fluctuation and insufficient response to levodopa. The patient's father who had the same mutation presented parkinsonism in old age. We also review the literature to address the broad clinical heterogeneity of Segawa disease and the influence of onset age on clinical presentation.

Case Report: Guitarist’s cramp as the initial manifestation of dopa-responsive dystonia with a novel heterozygous GCH1 mutation

“…Deficiency of GCH1, a rate-limiting enzyme in the biosynthetic pathway of tetrahydrobiopterin, is the most common and well-characterized condition that manifests as DRD 7 . In contrast to the childhood-onset GCH1-related DRD, adult cases often present parkinsonism followed by dystonia, and the movement problems progress slowly without diurnal variation 8 , 9 . Furthermore, a number of studies describing atypical or incompatible features of GCH1 deficient-DRD with variable age of onset exist 2 .…”

Recognizing Atypical Dopa-Responsive Dystonia and Its Mimics

“…2 This last type is more frequent in males, 15 with parkinsonism or tremor as the main or only clinical manifestation. 12,15,16 Some cases manifest both dystonia and parkinsonism. 17 One-third of patients with DRD have a family history of PD.…”

“…18,19 In young-onset cases, dystonia is initially markedly asymmetric, involving 1 lower or upper limb, and progressing in half of those without treatment, to a segmental or generalized dystonia. 1,3 Physical activity exacerbates clinical symptoms, 2,7 and diurnal fluctuation is a feature in 80%-94% of the cases 4,8,15 but decreases with age. 2 On neurologic examination, muscle stretch reflexes may be enhanced, but no other pyramidal signs should be present, as neither should cerebellar, sensory, or cognitive signs.…”

“…The second onset peak is in adulthood, between the third and sixth decades. 2 This last type is more frequent in males, 15 with parkinsonism or tremor as the main or only clinical manifestation. 12,15,16 Some cases manifest both dystonia and parkinsonism.…”

“…In young-onset cases, dystonia is initially markedly asymmetric, involving 1 lower or upper limb, and progressing in half of those without treatment, to a segmental or generalized dystonia. 1,3 Physical activity exacerbates clinical symptoms, 2,7 and diurnal fluctuation is a feature in 80%–94% of the cases 4,8,15 but decreases with age. 2…”