The current social status in adult patients with urea cycle disorders in Japan

Urea cycle disorders (UCDs) are inherited metabolic conditions that lead to inadequate nitrogen detoxification due to defects in urea cycle enzymes or transporters. The severity of UCDs is classified into two types: neonatal onset (severe) and late onset (often milder). This cross-sectional study aimed to assess the levels of intelligence, developmental disabilities, and social functioning in adult patients with UCDs in Japan. A total of 116 adult patients with UCDs were enrolled in the study, including 10 with carbamoyl phosphate synthetase 1 deficiency, 69 with ornithine transcarbamylase deficiency (OTCD), 17 with argininosuccinate synthetase deficiency, 9 with argininosuccinate lyase deficiency, 4 with arginase 1 deficiency, and 7 with Hyperornithinemia-Hyperammonemia-Homocitrullinuria syndrome. Of these, 25 (21.6 %) developed symptoms during the neonatal period (within 28 days after birth), while 86 (74.1 %) presented with symptoms after 28 days of age. The age of onset was unknown in 5 patients. This study included 111 surviving patients and 5 deceased patients (3 with OTCD and 2 with CPS1D). Fifty-three patients (45.7 %) experienced intellectual disabilities, while 48 (41.4 %) had non-intellectual disabilities. Additionally, learning disorders and communication disorders were common among many of the study participants. Sixty patients (51.7 %) graduated from regular high school, and most patients with intellectual disabilities graduated from special education schools. Almost half of the patients (51, 44.0 %) were able to obtain jobs, including simple tasks in supported workplaces, and received compensation for their work. Notably, more patients with OTCD could demonstrate higher social performance including experience of higher education and marriage. However, even OTCD patients without intellectual disabilities often struggled with specific neurobehavioral issues. This study provides information on the social situation of adult UCD patients and underlines the importance for clinicians, as well as society and communities, to understand the ongoing challenges faced by patients with UCDs in order to provide better support.