Amyotrophic onset in GCH1 dopa-responsive dystonia

Dopa-responsive dystonia (DRD) belongs to combined dystonia syndrome (dystonia-plus syndrome)1 which encompasses non-degenerative and neurometabolic disorders characterized by combination of dystonia as the prominent sign, with another movement manifestation. Parkinsonism and myoclonus are the main disturbances accompany dystonia in the combined dystonia syndrome. Dystonia with parkinsonism includes DRD [DYT5, tyrosine hydroxylase (TH), and sepiapterin reductase (SPR)], dopamine agonist-responsive dystonia, rapid-onset dystonia parkinsonism (DYT12), and early-onset dystonia with parkinsonism (DYT16). However, dystonia combined with myoclonus is just classified as myoclonus dystonia (DYT11).2 DRD can be inherited in either autosomal dominant or autosomal recessive patterns. The autosomal dominant inheritance results in the typical phenotype of DRD, known as DYT5 or Segawa disease, which is caused by heterozygous mutations of guanosine triphosphate (GTP) cyclohydrolase I gene (GCH1). Mutations of the TH and SPR genes are responsible for autosomal recessive types of DRD.3 DYT5 is represented as progressive lower limbs dystonia with childhood-onset at the common age of 2-5 years. It shows diurnal fluctuations, which are aggravated toward the evening and alleviated by sleeping. Excellent and sustained response to the low dose of levodopa is the marked feature of DYT5 disease. Additional parkinsonism and spasticity may present later in life.4 Moreover, hemiatrophy of the brain, body, or both has been reported in patients with DRD, associated with a biochemical lesion located in basal ganglia.5 However, focal atrophy and muscle weakness rarely accompanies DRD. Interestingly, we aimed to introduce weakness and focal muscle atrophy as the onset manifestations of DRD in an elderly man misdiagnosed for about 70 years.