From Coma to Genetic Insights: Identification of a Novel Pathogenic Variant in Chinese Neonatal CTLN1

Li-Jing Deng^1*Yaping Liu¹Kai Chen²Jianwu Qiu³Lu Chang¹Junxia Xia¹Yanrong Wang^1*

• ¹Shenzhen Third People’s Hospital, Shenzhen, China
• ²Shenzhen Samii International Medical Center, Shenzhen, China
• ³Yuebei People's Hospital, Shaoguan, China

Citrullinemia type I (CTLN1) is an autosomal recessive disorder caused by variants in the arginine succinate synthase gene (ASS1). These variants result in arginine succinate synthase deficiency, leading to a disruption of the urea cycle and hyperammonemia. To date, only a handful of CTLN1 cases have been reported in China. One neonate responded poorly 30 hours after birth and progressed to coma several hours later. Family history revealed that the neonate's older brother had also died a few days after birth. Biochemical tests on admission confirmed hyperammonemia and elevated levels of citrulline and urinary orotic acid-3. Genetic analysis revealed that the parents were carriers of two heterozygous variants in ASS1, c.910C>T(p.Arg304Trp) and c.839-1G>A, respectively. However, the splice site variant c.839-1G>A was not present in the control databases.Minigene analysis of the c.839-1G>A resulted in the product of r.839del [p.(Gly280Valfs*15)]. In conclusion, we have identified a case of CTLN1 and diagnosed a novel pathogenic variant in the ASS1 gene, c.839-1G>A, expanding the variant spectrum of ASS1. Currently, there are few reports of CTLN1 cases featuring such severe clinical manifestations and an onset at such a young age.