Objectives: To investigate genotype-phenotype characteristics and long-term prognosis of neonatal carbamoyl phosphate synthetase 1 (CPS1) deficiency among children through newborn screening in Zhejiang province.
Methods: The clinical and follow-up data of children with CPS1 deficiency detected through neonatal screening and confirmed by tandem mass spectrometry and genetic testing in Zhejiang Province Newborn Disease Screening Center from September 2013 to August 2023 were retrospectively analyzed.
Results: A total of 4 056 755 newborns were screened and 6 cases of CPS1 deficiency were diagnosed through phenotypic and genetic testing. Ten different variations of CPS1 genewere identified in genetic testing, including 2 known pathogenic variations (c.2359C>T and c.1549+1G>T) and 8 unreported variations (c.3405-1G>T, c.2372C>T, c.1436C>T, c.2228T>C, c.2441G>A, c.3031G>A, c.3075T>C and c.390-403del). All patients had decreased citrulline levels (2.72-6.21 μmol/L), and varying degrees of elevated blood ammonia. The patients received restricted natural protein intake (special formula), arginine and supportive therapy after diagnosis, and were followed-up for a period ranging from 9 months to 10 years. Three patients experienced hyperammonemia, and one patient each had attention deficit hyperactivity disorder, transient facial twitching and increased muscle tone. One patient died, while the other five surviving patients had normal scores of the Ages & Stages Questionnaires (ASQ) and Griffiths Development Scales up to the present time; 4 cases had combined height or weight lag and one case was normal in height and weight.
Conclusions: Low citrulline levels and hyperammonemia are common in CPS1 deficiency patients in Zhejiang. Most gene variants identified were specific to individual families, and no hotspot mutations were found. Early diagnosis through newborn screening and following standardized treatment can significantly improve the prognosis of the patients.
目的: 研究浙江省新生儿筛查发现的氨甲酰磷酸合成酶1（CPS1）缺乏症患儿的基因型和表型特点及长期预后。方法: 回顾性分析2013年9月至2023年8月浙江省新生儿疾病筛查中心采用干血斑串联质谱法筛查并联合基因检测诊断的CPS1缺乏症患者的所有筛查及临床随访资料。结果: 共筛查新生儿4 056 755名，联合表型及基因检测诊断CPS1缺乏症6例；基因检测结果发现CPS1 10种变异，包括2种已知致病性变异（c.2359C>T、c.1549+1G>T）及8种未报道变异（c.3405-1G>T、c.2372C>T、c.1436C>T、c.2228T>C、c.2441G>A、c.3031G>A、c.3075T>C、c.390-403del）。患儿初筛血瓜氨酸值均有下降（2.72~6.21 μmol/L），伴有血氨不同程度升高；诊断后给予限制天然蛋白摄入（特殊奶粉）、精氨酸及支持治疗，分别随访至9个月~10岁，有高氨血症发作3例，注意力缺陷多动、一过性口角抽动、肌张力增高各1例；除1例死亡，5例存活患儿的年龄与发育进程问卷及格里菲斯发育评估量表评分均正常，但合并身高或体重发育落后4例。结论: 浙江省CPS1缺乏症患儿表现为典型血瓜氨酸低、高氨血症生化改变；基因变异多数为家族特有，未发现热点突变。新生儿筛查早期诊断规范治疗患儿预后较好。.
Keywords: Carbamyl phosphate synthetase 1 deficiency; Follow-up studies; Genotype; Newborn screening; Phenotype; Prognosis.