Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report

Abstract

The aim of the present report was to describe the clinical presentation, diagnosis, and treatment of a case of carbamoyl phosphate synthetase 1 (CPS1) deficiency in a neonate, specifically, a 3 day-old female who visited Hunan Provincial People's Hospital due to anorexia and lethargy for 1 day. Physical and laboratory examination, and MRI were undertaken. Whole exome sequencing (WES) was applied for molecular etiology identification. Sanger sequencing was utilized to validate the variants detected by WES. Structural modeling was conducted for pathogenic analysis. Clinical examination revealed increased intracranial pressure, hyperammonemia, reduced citrulline, and increased glutamic acid levels. WES identified compound heterozygosity of c.713G>C, p.Arg238Pro and c.2339G>A, p.Arg780His in CPS1 (NCBI reference sequence, NM_001875.4) as candidate pathogenic variants. Sanger sequencing validated these variants. Structural modeling further confirmed the pathogenesis of these mutations. In conclusion, CPS1 deficiency in neonates is a serious condition that may be misdiagnosed due to severe infection. WES can be a helpful tool in facilitating the diagnosis of this disease.

New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis

“…CPS1 encodes a mitochondrial enzyme named carbamoyl-phosphate synthase 1 that catalyzes synthesis of carbamoyl phosphate from ammonia and bicarbonate. Mutations in this gene have been associated with metabolic deficiencies such as urea cycle disorder and hyperammonemia 53,54 . Individuals with a CPS1 deficiency can present with a wide range of clinical manifestations, including headache, behavioral or psychiatric problems, learning disabilities, sleep disorder, periodic vomiting, seizures, coma, and even death [55][56][57] .…”

Incidental occurrence of neutropenia in children hospitalised for COVID-19

“…Regarding the medical history of the neutropenic patients included in the study, only one infant showed a positive history for comorbidities: carbamoyl-phosphate synthetase 1 deficiency (CPS1-D), a disorder of urea cycle metabolism characterised by hyperammonemia that occurs a few days after birth [ 17 ]. However, this pathology is not associated with neutropenia or haematological disorders in general.…”