Clinical and genetic analysis of two children suspected for argininosuccinic aciduria

Objective To analyze the clinical and genetic features of two children suspected for arginylsuccinuria aciduria. Methods The patients were subjected to high-throughput sequencing using a gene panel. Results Both patients had high citrulline (87.37-156.10 μmol/L) measured by mass spectrometry/mas spectrometry (MS/MS) upon neonatal screening but had no symptoms. Two compound heterozygous variants of the ASL gene were detected in patient 1 (exon 6: c. 467C>T inherited from her father and exon 7: c. 556C>T inherited from her mother), among which c. 556C>T is novel. Patient 2 had mental retardation and two full siblings who had died of hyperammonemia before. Two compound heterozygosity variants of the ASL gene were detected (exon 3: c. 281G>T inherited from his father and intron: c. 208-15T>A inherited from his mother). Both were novel mutations. Conclusion Variants of the ASL gene probably underlie the argininosuccinic aciduria in the two patients. Above findings have enriched the spectrum of ASL mutations. Key words: Argininosuccinic aciduria; ASL gene; Tandem mass spectrometry; Gene panel