Pregnancy-related type citrullinemia type 1: A case report and literature review

Citrullinemia type 1 (CTLN1) is a rare autosomal recessive urea cycle disorder, without functional argininosuccinate synthase 1 (ASS1), mostly occurring in newborns and infants, but it has been reported as having an adult-onset in carriers of the pathogenic gene, and even more rarely, the onset of the disease is pregnancy related. Only 12 reported cases of onset during pregnancy and puerperium were reported since 1980. We herein report a case of gestational onset that resulted in patient death with a reported pathogenic mutation, c.421-2A>G, resulting in an amino acid change, splicing mutation, on exon7, in ASS1 gene, and a novel mutation, c.1046T>G, resulting in an amino acid change p.V349G, predicted by sorting intolerant from tolerant (SIFT), PolyPhen-2, Mutation Taster, Genomic Evolutionary Rate Profiling 2 (GERP++) and Rare Exome Variant Ensemble Learner (REVEL). This article provides an overview of the relationship between CTLN1 and pregnancy and discusses the possible mechanisms, clinical manifestations, and genetic characteristics of pregnancy-related onset.