The Current Status of Adult Patients With Urea Cycle Disorders in Japan: From the Nation-Wide Study

Urea cycle disorders (UCDs) are rare inherited metabolic diseases characterized by defective detoxification of nitrogen, leading to hyperammonemia and neurological complications. While pediatric UCDs have been extensively studied in Japan, data on adult patients remain limited. This study aims to evaluate the current status of Japanese adult UCD patients, hereby comparing long-term outcomes after neonatal/infantile or late onset in a new nationwide study investigating clinical manifestations and management. In total, we collected data of 116 adult UCD patients diagnosed and/or treated at various institutions, combining this new cohort (34 UCD patients between January 2010 and December 2022) with data from a previous nationwide study (82 UCD patients between January 2000 and March 2018). Among 116 adult UCD patients, ornithine transcarbamylase deficiency was the most common subtype (N = 69). Hyperammonemia occurred in 91.4% of patients, and intellectual disability was present in 50.0%. Patients generally showed reduced final height and BMI compared to Japanese controls, particularly among females and those with infantile-onset UCDs. Peak ammonia levels ≥ 360 μmol/L were significantly associated with intellectual disability. Liver transplantation (LT) was performed in 20 patients, and although it helped to avoid hyperammonemia, it did not statistically improve neurocognitive outcomes in patients with peak ammonia < 360 μmol/L. This study provides the first comprehensive overview of adult UCD patients in Japan, highlighting frequent growth impairment and variable cognitive outcomes. LT improves metabolic control but cannot prevent intellectual disability in all patients. These findings underscore the need for early diagnosis, individualized treatment strategies, and long-term follow-up into adulthood.