Genetic background and clinical characteristics of infantile hyperammonaemia

Abstract Purpose: This study was conducted to analyse the genetic spectrum and clinical characteristics of infantile hyperammonaemia (HA).Methods: Between January 2016 and June 2020, we enrolled patients with definitive genetic diagnosis of infantile HA at the Children’s Hospital of Fudan University. Based on the age of HA onset, patients were grouped into neonatal and post-neonatal subgroups to compare their genetic and clinical features. Results: Collectively, 136 pathogenic or likely pathogenic variants of the 33 genes were identified. Fourteen genes were reported with HA (42%, 14/33), with SLC25A13 and MUT being the top two detected genes. In contrast, 19 genes were not reported with HA (58%, 19/33), in which JAG1 and ABCC8 were the most frequently mutated genes. Compared with post-neonatal HA, neonatal HA patients presented with higher rates of organic acidemia (p = 0.001) and fatty acid oxidation disorder (p = 0.006), but a lower rate of cholestasis (p < 0.001). Neonatal HA patients had a higher ratio of peak plasma ammonia level ≥ 500 μmol/L (p = 0.003) and were more likely to receive precision medicine (p = 0.027); however, they had a refractory clinical course (p = 0.001) and poorer prognosis than the infantile group.Conclusions: There were significant differences in the genetic spectrum, clinical features, clinical course, and outcomes between infants with different HA onset ages.