探讨二酰甘油O-酰基转移酶(DGAT)1基因突变所致先天性腹泻与肠病(CODEs)患儿的临床及基因突变特点。

选择2020年12月，于华中科技大学同济医学院附属武汉儿童医院诊治的1例DGAT1基因突变所致CODEs患儿(以下以示区别称其为本例患儿)为研究对象。采用回顾性分析方法，分析本例患儿的临床病例资料，检索国内外数据库中关于DGAT1基因突变CODEs患儿相关研究的中、英文文献，总结该病患儿的临床及基因突变特点。本研究通过本院伦理委员会审查(审批文号：2021R045-E01)。监护人对本例患儿的诊治知情同意。

①本例患儿为女性，生后50 d时，因呕吐、腹泻就诊，入院查体发现其伴营养不良，实验室检查主要为低蛋白血症及高甘油三酯血症，基因检测结果为DGAT1基因exon 1：c.133delG(p.Asp45Thrfs*22)移码突变，为纯合突变，其父母均为DGAT1基因该位点突变携带者。本例患儿经低脂奶粉喂养及对症支持等治疗26 d后，临床治愈出院。其出院诊断为，CODEs(DGAT1基因纯合突变)。②文献检索获得关于DGAT1基因突变CODEs患儿相关研究文献为10篇，纳入CODEs患儿为29例，加上本例患儿共计纳入30例的分析结果如下。这30例患儿均于婴儿期起病(19例在新生儿期起病)，首发主要表现为腹泻(26/30，86.7%)，呕吐(19/30，63.3%)及营养不良(20/30，66.7%)；同时合并低蛋白血症(15/30，50.0%)和高甘油三酯血症(9/30，30.0%)；DGAT1基因突变位点主要包括g.13827T>C、c.629_631delCCT、c.314C>T及c.1202G>A等，主要突变类型为剪接突变、移码突变、错义突变等。对其治疗均以对症支持治疗为主，同时辅以低脂或无脂饮食喂养，大部分患儿临床症状改善。

本组CODEs患儿均由于DGAT1基因突变所致，多于新生儿期起病，主要临床表现为持续、严重、慢性腹泻与呕吐及营养不良，辅以低脂或无脂饮食可改善其临床症状。

To investigate characteristics of clinical and gene mutations of children with congenital diarrhea and enteropathies (CODEs) caused by diacylglycerol O-acyltransferase (DGAT)1 gene mutation.

A girl with CODEs caused by DGAT1 gene mutation treated in Wuhan Children′s Hospital, Tongji Medical College of Huazhong University of Science and Technology in December 2020 was selected as research subject. The clinical case data of the girl was retrospectively analyzed. Then Chinese and English literature related to CODEs caused by DGAT1 gene mutation in domestic and foreign databases were searched for literature review, and clinical and gene mutation characteristics of CODEs children were summarized. This study was reviewed by the Ethics Committee of our hospital (Approval No. 2021R045-E01). The guardians were informed and agreed to the diagnosis and treatment of this case.

① This case was a 50-day-old girl who was admitted to hospital due to vomiting and diarrhea, her physical examination showed accompanied with malnutrition. The main laboratory findings were hypoproteinemia and hypertriglyceridemia. Genetic test results showed frameshift mutation and homozygous mutation of DGAT1 gene exon 1: c. 133delG (p.Asp45Thrfs*22). Her parents were mutation carriers of this site of DGAT1 gene. After 26 days of feeding with low-fat milk powder and symptomatic support treatment, she was clinically cured and discharged. Her discharge diagnosis was CODEs (homozygous mutation of DGAT1 gene). ② The literature review obtained 10 pieces of relevant research literature on children with CODEs caused by DGAT1 gene mutation, and 29 children with CODEs were included. The analysis results of the total of 30 CODEs children included the girl in this study were as follows. Onset of CODEs among 30 children were in infancy (19 cases were in neonatal period), and primary manifestations were diarrhea (26/30, 86.7%), vomiting (19/30, 63.3%) and malnutrition (20/30, 66.7%). Meanwhile, accompanied with hypoproteinemia (15/30, 50.0%) and hypertriglyceridemia (9/30, 30.0%). The main mutation sites of DGAT1 gene included g. 13827T>C, c. 629_631delCCT, c. 314C>T and c. 1202G>A, and the main mutation types included splicing mutation, frameshift mutation, missense mutation, etc.. Their treatment mainly focused on symptomatic and supportive treatment, and feeding with a low-fat or fat-free diet, then the clinical manifestations of most children improved.

A comprehensive analysis showed all of 30 CODEs children of this study caused by DGAT1 gene mutation, most of them onset in neonatal period, and their main clinical manifestations are persistent, severe and chronic diarrhea, and vomiting and malnutrition. Feeding low-fat or fat-free diet can improve their clinical manifestations.