Genetic background and clinical characteristics of infantile hyperammonemia.

BACKGROUND

This study was conducted to analyze the genetic spectrum and clinical characteristics of infantile hyperammonemia.

METHODS

Between January 2016 and June 2020, we retrospectively enrolled infantile hyperammonemia patients with definitive genetic diagnosis at the Children's Hospital of Fudan University. Based on the age of hyperammonemia 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 hyperammonemia (42%, 14/33), with and being the top two detected genes. In contrast, 19 genes, which have not been previously reported with hyperammonemia, were detected (58%, 19/33), in which and were the most frequently mutated genes. Compared with post-neonatal hyperammonemia, neonatal patients with hyperammonemia 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). Patients with neonatal hyperammonemia 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 hyperammonemia onset ages.