Abstract: Objectives　To report the first Chinese case of early onset argininosuccinic aciduria. Methods A girl aged three days was admitted because of vomiting and lethargy from the second day of life. General laboratory examination, blood amino acids analysis, urine organic acids tests and gene studies were performed for the diagnosis. Results Severe hyperammonemia, liver dysfunction, metabolic acidosis, hypokalemia and hypocalcemia were found. Bood citrulline was extremely elevated (1098.12 μmol/L vs normal range 5 to 25 μmol/L), while blood arginine was decreased. Urine orotic acid, uracil and argininosuccinic acid were significantly elevated. Two known heterozygosis mutations on ASL gene, c.544C>T (p.R182X) and c.706C>T (p.R236W), confirmed the diagnosis of argininosuccinic aciduria. Unfortunately, protein-restricted diet with L-arginine supplement showed no effect. The patient died at the 23th day of life. Conclusions Argininosuccinic aciduria is a severe inherited metabolic disorder. Clinical diagnosis is difficult. It is characterized biochemically by severe citrullinemia. Urine organic acids analysis and ASL gene analysis are important for the differential diagnosis. In this study, a case of neonate death due to early-onset argininosuccinic aciduria was diagnosed by post-mortem investigation. ASL gene study is helpful for the genetic counseling and prenatal diagnosis of the disease.