Clinical, Biochemical, and Molecular Analyses of Three Patients with Urea Cycle Disorders in China

Urea cycle disorders (UCDs) are rare inherited metabolic diseases that can cause severe hyperammonemia and neurological damage. This study aimed to characterize the clinical, biochemical, and molecular features of three Chinese patients with UCDs and identify pathogenic variants through genetic analysis.

Blood tandem mass spectrometry and urinary gas chromatography-mass spectrometry were performed on three children diagnosed with UCDs. Next-generation sequencing and Sanger sequencing were performed on blood samples from the probands and their parents. Clinical data and other laboratory results were retrospectively collected from medical records. In silico and structural analyses were performed for three of the five identified variants.

The three probands exhibited clinical and biochemical features characteristic of UCDs. Genetic analysis confirmed five diagnostic variants, including two novel variants. These variants caused three types of UCDs: ornithine transcarbamylase deficiency (OTCD), carbamoyl phosphate synthase 1 deficiency, and argininosuccinate lyase deficiency (ASLD). In silico and structural analyses of three variants (OTC:c.1006-1G>T, CPS1:c.729+1G>A, and ASL:c.370T>C) suggested that all three may impair enzyme function or stability, although experimental validation is required.

We characterized the clinical, biochemical, and molecular features of three Chinese patients with UCDs. Two novel variants expand the known mutational spectra of OTCD and ASLD.