Two novel mutations in the CPS1 gene of a newborn with carbamoyl phosphate synthetase 1 deficiency identified by next-generation sequencing

Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare autosomal recessive hereditary disease which usually presents as lethal hyperammonemia. Here we report the case of a newborn infant with lethal hyperammonemia. Blood liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed increased concentrations of alanine, glutamine and histidine. Urine gas chromatography-mass spectrometry (GC/MS) showed increased levels of organic acids, while uracil and whey acid were not detected. Subsequent new generation sequencing (NGS) identified two heterozygous mutations in CPS1 gene. Both of them were identified in his parents. One was c.446T>C; p.Leu149Ser, in the 4 exon of CPS1. The other was C.2023delT; p.Cys675fs, in the 17 exon of CPS1. These two novel heterozygous mutations had not been reported previously. Early diagnosis and timely intervention are very important to improve clinical outcome. The new CPS1 gene mutation broadens the spectrum of CPS1 phenotypes. NGS is a credible way in complex diseases without a specific phenotype.