Incidence and Prevalence Rate of Segawa Disease in Japan

Background: Segawa disease is a very rare inherited disease, which is characterized by dopa-responsive dystonia and diurnal fluctuation. Dysfunction of GTP cyclohydrolase I (GTPCHI) due to mutations of the enzyme-coding gene, GCH1, reduced the production of neopterin and biopterin, and this induced a shortage of dopamine in the central nervous system.

Method: We examined 137 patients who suffered dystonia and/or other involuntary movements, from January 2012 to December 2016. We measured the neopterin and biopterin content in these patients. Genetic analysis of GCH1, which encoded GTPCHI, was also performed in 50 patients.

Results: Twenty-two patients had mutations in GCH1 and were diagnosed with Segawa disease. These patients comprised 18 females and 4 males. The average age of patients who underwent genetic analysis was 19.35 years (Range: 7 to 62). Most of the patients who were diagnosed as adults showed dystonic symptoms from a very young age. The mutations detected in the GCH1 of patients in this study included six missense mutations, three frame-shift mutations, one nonsense mutation, four mutations in introns around exons, and four large exon deletions. Three families had their own unique mutation; however, no common mutation was observed in other patients. In this study, we examined patients from 32 of the 47 prefectures in Japan (total population of these areas was 106,058,400 in 2016). The calculated incidence rate of Segawa disease was 4.1/100,000,000 per year in this study. The prevalence rate was considered 1.6/1,000,000 when the average of duration of this disease was 40 years.

Conclusion: Over the course of five years, we genetically diagnosed patients with Segawa disease. No common mutation was observed. The incidence rate was 4.1 per hundred million people per year and the prevalence rate was 1.6 per million people in Japan.