Objective: To clarify clinical features of Segawa Disease (SD) in Japan.

Background: Prof Segawa discovered SD 50 years ago, and GCH-1 gene mutations were linked to this condition 30 years ago. Lifetime management of SD requires precise and long-term analysis of clinical features.

Method: The national survey URL google form with 45 questions was announced in mailing lists of the Japanese Society of Adult/Child Neurology from 12/2022 to 10/2023. Our ethics committee approved this study (SMNCC22-03R2). In first survey, 121 child/adult neurologists responded, and 20 (4 adult and 16 child) neurologists’ consented to a second survey. Patient records (124) were collected, and 97 patients positive for GCH1 were analyzed.

Results: Q1 Onset mean age :6±5.3 y (1-34)   

Q2 Current mean age :30 ±19y (4-88)

Q3 Gender :81.4% female   

Q4-5 GCH1 genetic testing :110 patients; 97 (88%) positives.

Q6-7 family history :70.1% 

Q8-13 Initial symptoms :focal dystonia (92.8%), writer’s cramp (5.2%), with 86.6% in the legs and 9.3% in the arms; 91.8% exhibited diurnal fluctuation. Also 20.6% were comorbid with psychological problems

Q14  Misdiagnosed before confirmed SD : 54.6% 

Q15 Consultation orthopedic :55.7%

Q16 Orthopedic surgery :10.3% 

Q17-22 (n) Normal MRI: 57/58 (number of patient examined), normal DAT imaging :11/13, normal EEG:43/48, dystonia in sEMG :39/44, decreased neopterin/biopterin in cerebral spinal fluid :22/27.

Q23-24 Initial treatment: plain levodopa monotherapy (75.3%), dopa-decarboxylase inhibitor (DCI)(18.6%).

Q25-28 Current symptoms (under treatment) : focal dystonia (22.7%)  writer’s cramp (3.1%), with 14.4% in the legs and 5.2% in the arms. Only 23.7% exhibited diurnal fluctuation. Q29-30 Current treatment: plain levodopa (25.8%) , DCI (73.2%).

Q31 Current motor symptoms: minimal motor symptoms(n=14).

Q32-33 Other  treatment :None (87.6%).   

Q34 Current psychological problems :36.1%.

Q35-36 Current states :students (34.0％), workers (33.0％), housewives (13.4%)

Q37 Medications for non-motor symptoms: 18.6%

Q38 Menstruation exacerbation: no (45.3%), yes (17.3%), not asked (37.7%)

Q39-44 Pregnancy: pregnant (n=30); suffered miscarriages (5); aggravated dystonia during pregnancy (13), with occurring after birth (6); postpartum depression (1)

Conclusion: We clarified the long clinical course from onset to current SD. Menstruation and pregnancy status were important, and greater consideration of residual motor and psychological symptoms under L-dopa treatment is required

Table 1. Details of answer

Table 2. Initial and current symptoms

Fig.1 Differences in age of onset by site (n)

Fig.2 Age-related changes in TH and SD features

References: Segawa M, Ohmi K. Itoh S.et al. Childhood basal ganglia disease with remarkable response to L-Dopa ‘hereditary basal ganglia disease with marked diurnal fluctuation’. Shinryo (Tokyo). 1971; 24:667-672 [in Japanese]
Segawa M, Hosaka A, Miyagawa F, et al.Hereditary progressive dystonia with marked diurnal fluctuation Eldridge, R. ∙ Fahn, S. Raven Press, New York, in: Advances in neurology. 1976; 215-233
Segawa M. Dopa-responsive dystonia. Handb Clin Neurol. 2011;100:539-57.
Ichinose H, Ohye T, Takahashi E et al. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nat Genet. 1994;8:236-42.
Segawa M. Hereditary progressive dystonia with marked diurnal fluctuation. Brain Dev. 2000 Sep;22 Suppl 1:S65-80.
Hoshino K, Kawai M, Nagao Y, et al. National Survey of Segawa Disease in Japan. 18th International Child Neurology Congress. 2024.Capetown

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