Chen Xihui, Yuan Lijuan, Sun Mao, Liu Qingbo, Wu Yuanming
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Center for DNA Typing, Fourth Military Medical University, Xi'an, China.
J Clin Lab Anal. 2018 Jun;32(5):e22375. doi: 10.1002/jcla.22375. Epub 2018 Jan 4.
Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare autosomal recessive disorder of the urea cycle, mostly characterized by hyperammonemia and the concomitant leukodystrophy. The onset of CPS1D can be at any age, and the clinical manifestations are variable and atypical. Genetic tests are indispensable for accurate diagnosis of CPS1D on the basis of biochemical tests.
Blood tandem mass spectrometric analysis and urea organic acidemia screening were performed on a Chinese neonatal patient with low activity, recurrent seizures, and hyperammonemia. Next-generation sequencing and Sanger sequencing were followed up for making a definite diagnosis. Bioinformatics tools were used for the conservation analysis and pathogenicity predictions of the identified mutations.
Increased lactate in urea and decreased citrulline in blood were detected in the patient. Two novel mutations (c.173G>T, p.G58V in exon 2 and c.796G>A, p.G266R in exon 8) in CPS1 identified in the neonatal patient were found through coseparation verification. Both of the two mutations were predicted to be deleterious, and the two relevant amino acids exerted highly evolutionarily conserved. The final diagnosis of the patient was compound heterozygous CPS1D.
This study described the specific clinical characteristics and the variations of physiological and biochemical indices in a Chinese neonatal patient with CPS1D, which facilitated the diagnosis and mechanism research of the disease. Two novel causative missense mutations were identified, which enriched the mutation spectrum of CPS1D in China and worldwide. Advice of prenatal diagnosis was given to the family for a new pregnancy.
氨甲酰磷酸合成酶1缺乏症（CPS1D）是一种罕见的常染色体隐性尿素循环障碍疾病，主要特征为高氨血症及伴随的脑白质营养不良。CPS1D可在任何年龄发病，临床表现多样且不典型。基于生化检测的基础上，基因检测对于CPS1D的准确诊断不可或缺。
对一名有低活性、反复惊厥和高氨血症的中国新生儿患者进行血串联质谱分析和尿素有机酸血症筛查。随后采用二代测序和桑格测序进行明确诊断。利用生物信息学工具对鉴定出的突变进行保守性分析和致病性预测。
该患者检测到血中尿素乳酸升高和瓜氨酸降低。通过共分离验证，在该新生儿患者中鉴定出CPS1的两个新突变（外显子2中的c.173G>T，p.G58V和外显子8中的c.796G>A，p.G266R）。预测这两个突变均有害，且两个相关氨基酸具有高度进化保守性。该患者最终诊断为复合杂合型CPS1D。
本研究描述了一名中国新生儿CPS1D患者的具体临床特征以及生理生化指标变化，有助于该病的诊断和机制研究。鉴定出两个新的致病错义突变，丰富了中国及全球CPS1D的突变谱。并为该家庭下一胎妊娠提供了产前诊断建议。
