Genetic diagnosis of a Chinese pedigree affected with neonatal argininosuccinic aciduria

Objective To explore the genetic basis of a neonate with argininosuccinic aciduria (ASA). Methods A neonate with lethargy and food refusal was admitted. The patient had myoclonus, myasthenia, uroschesis, irregular breathing and paroxysmal ventricular tachycardia, and died at 75 hours after birth. Laboratory test showed marked increase in blood ammonia (1249.8 μmol/L). Peripheral blood samples of the patient, her parents and sister were collected and subjected to trio whole-exome sequencing. Results Whole-exome sequencing revealed that the patient has carried compound heterozygous mutations of the argininosuccinate lyase (ASL) gene, namely c. 425(exon5)_c.426(exon5) insAGCTCCCAGCT (p.Thr142Thrfs*37) and c. 626(exon8)delT (p.Leu209Argfs*42). The patient was diagnosed as ASA caused by ASL gene mutations. Her parents and her elder sister were heterozygous carriers of the above mutations and had a normal phenotype. Conclusion ASA is a severe congenital genetic metabolic disease and can manifest as onset of hyperammonemia in neonates. The clinical diagnosis is difficult and ASL gene testing may be helpful. Key words: Argininosuccinic aciduria; ASL gene; Hyperammonemia; Neonate