新生儿早发型丙酸血症1例临床特征及遗传学分析并文献复习

Clinical Characteristics and Genetic Analysis of a Case of Neonatal Early-Onset Propionate Acidemia and Literature Review

摘要: 目的：探讨1例早发型丙酸血症患儿的临床表型及遗传学特征。方法：选取2022年11月收治于青岛大学附属医院的1例丙酸血症患儿为研究对象，分析其临床资料，对其进行家系全外显子组基因检测，用Sanger测序分析对候选变异进行验证。结果：女性患儿，生后73小时逐渐出现反应差、嗜睡、拒乳、喂养困难入院。血尿遗传代谢检查提示甲基丙二酸血症、丙酸血症、酮尿；全外显子组基因检测提示患儿携带PCCA基因复合杂合变异：c.1900-1G>A (splicing)和c.575del (p.Ile192ThrfsTer7)，分别遗传自其母亲与父亲，这两个基因变异均未见报道，根据美国医学遗传学与基因组学学会相关指南均评估为致病变异。结论：PCCA基因c.1900-1G>A (splicing)和c.575del (p.Ile192ThrfsTer7)复合杂合变异可能是导致患儿发生丙酸血症的遗传学病因。这两个新变异的检出扩大了PCCA基因的变异谱，为患儿的临床诊断和家系遗传咨询提供了重要的依据。

Abstract: Objective: Exploring the clinical manifestations and genetic characteristics of a child with ear-ly-onset propionaemia. Methods: The clinical data of a newborn with propionic acidemia who visited our hospital on November 17, 2022 was collected. A trio-exome sequencing was performed on them. Candidate variants were validated using Sanger sequencing analysis. Results: The patient is a fe-male who gradually experiences poor response, somnolence, refusal to breastfeed, and difficulty feeding 73 hours after birth. Blood test shows hyperammonemia, hyperkalemia, hyperglycemia, metabolic acidosis; Brain magnetic resonance imaging shows symmetrical strip like DWI high sig-nal shadows in the bilateral corticospinal tract, bilateral thalamus, brainstem, and bilateral cere-bellar hemispheres, consistent with metabolic or toxic diseases. The right cerebellar hemisphere has hemorrhagic foci and intraventricular hemorrhage; Hematuria genetic metabolism examina-tion indicates methylmalonic acid, propionic acidemia, ketonuria; Trio-complex heterozygous vari-ant of the PCCA gene: c.1900-1G>A (splicing) and c.575del (p.Ile192ThrfsTer7), which are inherited from their mother and father, respectively. Among them, c.1900-1G>A (splicing) and c.575del (p.Ile192ThrfsTer7) have not been reported in the past, and according to the relevant guidelines of the American Society of Medical Genetics and Genomics, they are determined to be pathogenic var-iants with unknown significance. Conclusion: The complex heterozygous variants of the PCCA gene c.1900-1G>A (splicing) and c.575del (p.Ile192ThrfsTer7) may be the cause of the disease in the pa-tient. The detection of 575del (p.Ile192ThrfsTer7) and c.1900-1G>A (splitting) expanded the muta-tion spectrum of PCCA gene, providing an important basis for clinical diagnosis and family genetic counseling of children.