Objective: To analyze clinical phenotype of recent variation of Segawa disease（GCHⅠ deficiency, DYT5a）in Japan.

Background: Segawa Disease（SD）is  major  dystonia in children found by Prof.Masaya Segawa in 1970. In the half century, over 250 cases were reported in Japan, however recently GCHⅠ mutations were identified in clinically atypical cases one and another. Classical SD initially reported by Prof.Segawa reveals postural dystonia with remarkable diurnal fluctuation and responds to levodopa dramatically. In contrast, atypical SD appears action dystonia or other involuntary movements later in adulthood and effect of levodopa is incomplete and diagnosed with positive GCH1 mutation.

Method: Fourteen cases of SD (6 males and 8 females) visiting our clinic from Jan,2015 to 2020 were analyzed retrospectively. We classified cases into three groups, classical type of SD (Classical) ,  Atypical type (Atypical),  suspected SD (Suspected)  because of dopa responsive and having family history SD but negative of GCHⅠ mutation.

Results: ‘Classical’ was 6 (M:F 3:3), ‘Atypical’ 5 (M:F 2:3), ‘Suspected’  3 (M:F 1:2). Age of onset : 6.5y±1.92 (5-10), 9.2y±5.3(6-20),7.7y±4.3(0-13) as ‘Classical’ ‘Atypical’ ‘Suspected’ ‘respectively.  Initial symptom: postural dystonia of legs in all cases. ‘Atypical’  developed  other involuntary movement later.  Diurnal fluctuation: 12/13 cases. Family history: No consanguinity, no Parkinson disease. Two brothers and tow sisters included. Comorbidities: Autism spectrum disorder 1, psychomotor developmental delay 1, hydrocephalus 1, schizophrenia 1 and anxiety disorder 1. Medication: levodopa in 6, (Initial dose:1-7mg/kg, median 1.7mg/kg),L-dopa/carbidopa in 7 (Initial dose:0.9-7.4 mg/kg, median 2.4mg/kg). Examinations : 5/7 decreased memory guided saccade recorded by Eye-Link . One case of ‘Atypical’ showed decrease of DaT SPECT.

Conclusion: ‘Classical’ SD is considered as narrow spectrum which appears postural dystonia of legs in early childhood with diurnal fluctuation and responds to levodopa dramatically and continuously. In contrast, diagnosis of ‘Atypical’ SD depends on GCHⅠ gene analysis because of atypical coarse and incomplete response to levodopa. ‘Suspected SD’ is consider other unkown pathology. In this study, there are no PD patients in all family. However PD with GCHⅠ mutation would be adult phenotype GCHⅠ deficiency. We should consider PD with GCHⅠ mutation together in near future.

References: Segawa M, Adv Neurol. 1976;14:215-33.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/recent-clinical-variation-of-segawa-disease-in-japan/