探讨迟发型丙酸血症(PA)患儿的临床特点和基因突变特点。

选择2016年8月31日在南京医科大学附属妇产医院经剖宫产分娩娩出的1例男性迟发型PA患儿为研究对象。收集本例患儿的干血斑串联质谱(MS/MS)、尿滤纸片气相色谱质谱(GC/MS)及家系基因检测结果等临床资料，回顾性分析患儿的病史、串联质谱检测结果、遗传代谢病Panel高通量测序结果及随访结果。本研究遵循的程序符合南京市妇幼保健院人体试验委员会制定的伦理学标准，并得到该伦理委员会批准。

①本例PA患儿无特殊临床症状，干血斑MS/MS检测结果提示丙酰肉碱(C3)水平为2.79～7.03 μmol/L，GC/MS检测结果提示尿液3-羟基丙酸水平为0～129.48 μmol/L。②基于高通量测序技术的基因Panel结果显示，PCCA基因检测到2个致病突变(c.802C>T、c.827delG)。其中c.802C>T点突变导致氨基酸序列发生p.Arg268Cys突变，该突变位点遗传自患儿母亲；此外c.827delG为移码突变，该突变位点遗传自患儿父亲，该突变导致氨基酸序列发生p.Gly276ValfsX46突变，为未报道的新突变。③随访结果显示，患儿肝、肾功能正常。④本例患儿最终诊断为迟发型PA。

移码突变c.827delG是PCCA基因未报道的新突变，新生儿MS/MS、GC/MS检测结合Panel高通量测序技术，在迟发型PA的诊断中具有重要的应用价值。

To investigate the clinical characteristics and gene mutations of delayed propionic academia (PA).

One male patient with delayed PA who was hospitalized in Nanjing Maternity and Child Health Care Hospital on May 20, 2016, was chosen as study object. The clinical data of the patient was analyzed retrospectively, including results of tandem mass spectrometry (MS/MS) detection, gas chromatography-mass spectrometry (GC/MS) detection, and clinical manifestations. The DNA was extracted from the blood samples of child and his parents, and the Panel high-throughput sequencing technology was used to amplify the mutations. The study protocol was approved by the Ethnical Review Board of Investigation in Human Beings of Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University.

① There were no specific clinical symptoms of this patient. The concentration of propionyl carnitine (C3) ranged from 2.79-7.03 μmol/L, urine 3-hydroxy propionic acid ranged from 0-129.48 μmol/L. ②Two mutations (c.802C>T, c. 827delG) in PCCA gene were confirmed. The gene detection results showed these two mutations were inherited from father [c.827delG(p.Gly276ValfsX46)] and mother [c.802C>T(p.Arg268Cys)], respectively. The frameshift mutation in PCCA gene (c.827delG) was novel. ③ The follow-up results of liver function and renal function showed normal.

It is important to use a combination of MS/MS, GC/MS and Panel high-throughput sequencing technology in the diagnosis of delayed PA. The mutation c. 827delG is a specific novel mutation of PCCA gene, expanding its mutation spectrum.