Prenatal diagnosis of citrullinemia type 1: A Chinese family with a novel mutation of the ASS1 gene

Abstract Background Argininosuccinate synthetase deficiency (citrullinemia type 1) is a rare autosomal recessive disorder of the urea cycle characterized by elevated concentrations of citrulline, ammonia, and orotic acid, manifesting with acute hyperammonemic crises, usually early in life, with concurrent neurologic deterioration. Only a few cases of citrullinemia type 1 have been documented from mainland China. Prenatal diagnosis has not been performed. Methods A Chinese family affected by citrullinemia type 1 was studied. The proband, a girl, was the second child born to a non-consanguineous couple. Her elder brother died at 19 months due to coma and liver dysfunction of unknown cause. The proband was admitted because of severe mental retardation and lethargy at the age of 15 months. Initial laboratory results revealed hyperammonaemia, hypercitrullinemia (928.771 μmol/L, normal 5.0–25.0 μmol/L) and orotic aciduria, supporting the diagnosis of citrullinemia type 1. Subsequently, the mother presented at 15 weeks of pregnancy seeking for genetic counseling and prenatal diagnosis. ASS1 gene in the blood leukocytes of the family members and amniocytes was performed by direct sequencing. Results On the ASS1 gene of the proband, a novel mutation, T1009C (C337R), and a previously reported mutation G847A (E283K) were identified. Each parent carries one of two mutations. G847A and T1009C mutations were detected in amniocytes, as same as the proband of the family. The result revealed that the fetus was affected by argininosuccinate synthetase deficiency. The parents chose to have a termination of the pregnancy. Conclusions Prenatal diagnosis for citrullinemia type 1 was performed in a Chinese family using gene analysis. T1009C (C337R), a novel mutation of ASS1, was identified.