Urea cycle disorders (UCDs) are inherited
metabolic diseases causing
hyperammonemia by defects in
urea cycle
enzymes or transporters.
Liver transplantation (LT) currently is the only curative treatment option until novel
therapies become available. We performed a nationwide questionnaire-based study between January 2000 and March 2018 to investigate the effect of LT in patients with UCDs in Japan. A total of 231 patients with UCDs were enrolled in this study. Of them, a total of 78 patients with UCDs (30 male and 16 female
ornithine transcarbamylase deficiency (OTCD), 21
carbamoyl phosphate synthetase 1 deficiency (CPSD), 10
argininosuccinate synthetase deficiency (ASSD) and 1
arginase 1 deficiency (ARGD)) had undergone LT. Concerning the maximum blood
ammonia levels at the onset time in the transplanted male OTCD (N = 28), female OTCD (N = 15), CPSD (N = 21) and ASSD (N = 10), those were median 634 (IQR: 277-1172), 268 (211-352), 806 (535-1382), and 628 (425-957) μmol/L, respectively. The maximum blood
ammonia levels in female OTCD were thus significantly lower than in the other UCDs (all P < .01). LT was effective for long-term survival, prevented recurrent
hyperammonemia attack, and lowered baseline blood
ammonia levels in patients with UCDs. LT had limited effect for ameliorating neurodevelopmental outcome in patients with severe disease because
hyperammonemia at the onset time already had a significant impact on the brain. Patients with ASSD may be more likely to survive without
cognitive impairment by receiving early LT despite severe neonatal
hyperammonemia ≥ 360 μmol/L. In patients with neonatal onset OTCD or CPSD, there may be additional factors with adverse effects on the brain that are not improved by LT.