Abstract
BACKGROUND: Ornithine carbamyltransferase deficiency (OTCD) is the most common urea cycle disorder disease. Neonatal-type cases usually involve a serious condition, including the complete loss of ornithine carbamyltransferase (OTC) enzyme activities. CASE DESCRIPTION: Case 1: A 3-day-old boy was hospitalized due to decreased muscle tone over three days, 10 hours of dyspnea, and two instances of convulsions. Diagnostic tests showed elevated blood ammonia levels, decreased citrulline concentration via mass spectrometry (MS/MS), and increased orotic acid observed by gas chromatography-mass spectrometry (GC/MS), while uracil was normal. Head ultrasound revealed abnormal brain parenchyma, indicating brain damage. Whole exon gene sequencing detected a new pathogenic mutation [c. 961T > C (p.Ser321Pro)] in the OTC gene, and the mother was identified as a carrier of this mutation. Case 2: A 3-day-old boy was admitted to our hospital because of "heart failure". The patient's blood ammonia was significantly increased; the MS/MS results showed that citrulline concentration decreased; the GC/MS results demonstrated that orotic acid was significantly increased; uracil was normal; and head magnetic resonance imaging (MRI) + diffusion-weighted imaging (DWI) + magnetic resonance spectroscopy (MRS) showed abnormal signals in the brain, with partial cystic malacia. Clinical exon gene sequencing showed that the 500 bp short interspersed nuclear elements (SINE) element may have been inserted into exon 5 of the OTC gene, which was inherited from his mother; this has not been reported previously in the literature. Although the blood ammonia of two patients decreased, they both died after giving up because of serious nervous system damage. In addition, a total of 62 neonatal OTCD patients were found in the literature. The clinical manifestations of these patients were not specific. The MS/MS results of 81% of neonatal OTCD patients showed that the concentration of citrulline was decreased. About 91% showed a significant increase in orotic acid, mutation sites were detected in 100% of the patients, and the prognosis was poor. CONCLUSIONS: This study improves our understanding of the clinical characteristics and OTC gene mutation sites of neonatal OTCD cases. c.961T>C and c.ins SINE? were identified as new mutations. The clinical manifestations of neonatal OTCD patients lack specificity, and the clinical and biochemical characteristics combined with gene detection are important for the diagnosis of OTCD.