Long‐term outcome of urea cycle disorders: Report from a nationwide study in Japan

Abstract

Urea cycle disorders (UCDs) are inherited metabolic disorders with impaired nitrogen detoxification caused by defects in urea cycle enzymes. They often manifest with hyperammonemic attacks resulting in significant morbidity or death. We performed a nationwide questionnaire-based study between January 2000 and March 2018 to document all UCDs in Japan, including diagnoses, treatments, and outcomes. A total of 229 patients with UCDs were enrolled in this study: 73 males and 53 females with ornithine transcarbamylase deficiency (OTCD), 33 patients with carbamoylphosphate synthetase 1 deficiency, 48 with argininosuccinate synthetase deficiency, 14 with argininosuccinate lyase deficiency, and 8 with arginase deficiency. Survival rates at 20 years of age of male and female patients with late-onset OTCD were 100% and 97.7%, respectively. Blood ammonia levels and time of onset had a significant impact on the neurodevelopmental outcome (P < .001 and P = .028, respectively). Hemodialysis and liver transplantation did not prevent poor neurodevelopmental outcomes.While treatment including medication, hemodialysis, and liver transplantation may aid in decreasing blood ammonia and/or preventing severe hyperammonemia, a blood ammonia level ≥ 360 μmol/L was found to be a significant indicator for a poor neurodevelopmental outcome. In conclusion,

Role of liver transplantation in urea cycle disorders: Report from a nationwide study in Japan

“…25 We previously reported that neonatal onset UCD patients, who often develop severe hyperammonemia (≥360 μmol/L), should receive LT to prevent frequent hyperammonemia attacks and to improve their QOL, and that even such patients may achieve almost normal neurodevelopmental outcome after LT. 3 In the present study, there is no significant difference in long-term survival between UCD patients with and without LT because the long-term survival in UCDs patients without LT also is improved compared to our previous study. 26 In the recent years, clinicians in Japan have more information on UCDs and novel treatments such as sodium phenylbutyrate and citrulline were more commonly administered. Long-term management skills for patients with UCDs were progressed.…”

“…Improved hemodialysis techniques in neonates have resulted in a more widespread use of this highly efficient modality. 26 For long-term neurodevelopmental outcome, patients with hyperammonemia ≥360 μmol/L at the onset time may not achieve normal neurodevelopmental outcome even after receiving LT likely because of the impact of initial blood ammonia levels on brain. However, this study suggested that ASSD patients when receiving early LT, and despite severe hyperammonemia (≥360 μmol/L) at the onset time, might be expected to achieve normal neurodevelopmental outcome.…”

“…Long‐term management skills for patients with UCDs were progressed. Improved hemodialysis techniques in neonates have resulted in a more widespread use of this highly efficient modality 26 …”

Clinical manifestation and long‐term outcome of citrin deficiency: Report from a nationwide study in Japan

“…In 2018, we invited 1009 medical institutions, including the respective departments of pediatrics, endocrinology and metabolism, neonatology, genetics, and transplant surgery, to participate in a questionnaire survey regarding patients with citrin deficiency (Data S1). Each institution was a medical center that serviced a local area in Japan and had approximately 300 beds, based on previous survey reports 21 . The questionnaire aimed to establish whether healthcare professionals had diagnosed or provided medical treatment to patients with citrin deficiency.…”

“…Each institution was a medical center that serviced a local area in Japan and had approximately 300 beds, based on previous survey reports. 21 The questionnaire aimed to establish whether healthcare professionals had diagnosed or provided medical treatment to patients with citrin deficiency. Of the 1009 institutions, 731 (72%) responded, and 104 confirmed that patients with citrin deficiency had been diagnosed and/or treated at their facility.…”