Advances in Evaluation of Chronic Diarrhea in Infants.
Advances in Evaluation of Chronic Diarrhea in Infants.
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DOI：
10.1053/j.gastro.2018.03.067
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发表时间：
2018-06
期刊：
影响因子：
29.4
通讯作者：
PediCODE Consortium
中科院分区：
文献类型：
--
作者：
Thiagarajah JR;Kamin DS;Acra S;Goldsmith JD;Roland JT;Lencer WI;Muise AM;Goldenring JR;Avitzur Y;Martín MG;PediCODE Consortium
腹泻在婴儿（2岁以下儿童）中很常见，通常是急性的，如果是慢性的，通常是由过敏引起的，偶尔是由传染性病原体引起的。先天性腹泻和肠病（CODE）是婴儿慢性腹泻的罕见原因。CODE的评估是一个漫长的过程，很少导致明确的诊断。然而，基因组分析和模型系统的发展增加了我们对CODE发病机制的理解。随着这些进展，需要一种新的诊断方法。我们提出了一种修正的方法来确定婴儿腹泻的原因，包括CODE，基于粪便分析，组织学特征，对饮食调整的反应和基因检测。在排除婴儿腹泻的常见原因后，通过分析粪便特征（水样、脂肪或血性）和组织学特征（如肠活检中的绒毛与隐窝比例）进行评估。因消化、吸收、营养和电解质转运缺陷或肠内分泌细胞发育或功能缺陷而导致CODE的婴儿绒毛与隐窝比例正常;肠上皮细胞结构缺陷或免疫介导的疾病导致绒毛与隐窝比例和形态异常。在评估的早期阶段进行全外显子组和基因组测序可以减少明确诊断CODE所需的时间，或导致识别与这些肠病相关的新变体。基因突变的功能效应可以在模型系统中进行分析，如肠样细胞或诱导多能干细胞，并通过基因编辑程序的最新进展得到促进。新的CODE疾病的表征和研究将改善患者的管理，并促进我们对肠粘膜上皮细胞和其他细胞的理解。
Diarrhea is common in infants (children less than 2 years of age), usually acute, and, if chronic, commonly caused by allergies and occasionally by infectious agents. Congenital diarrheas and enteropathies (CODEs) are rare causes of devastating chronic diarrhea in infants. Evaluation of CODEs is a lengthy process and infrequently leads to a clear diagnosis. However, genomic analyses and the development of model systems have increased our understanding of CODE pathogenesis. With these advances, a new diagnostic approach is needed. We propose a revised approach to determine causes of diarrhea in infants, including CODEs, based on stool analysis, histologic features, responses to dietary modifications, and genetic tests. After exclusion of common causes of diarrhea in infants, the evaluation proceeds through analyses of stool characteristics (watery, fatty, or bloody) and histologic features, such as the villus to crypt ratio in intestinal biopsies. Infants with CODEs resulting from defects in digestion, absorption, transport of nutrients and electrolytes, or enteroendocrine cell development or function have normal villi to crypt ratios; defects in enterocyte structure or immune-mediated conditions result in an abnormal villus to crypt ratios and morphology. Whole-exome and genome sequencing in the early stages of evaluation can reduce the time required for a definitive diagnosis of CODEs, or lead to identification of new variants associated with these enteropathies. The functional effects of gene mutations can be analyzed in model systems such as enteroids or induced pluripotent stem cells and are facilitated by recent advances in gene editing procedures. Characterization and investigation of new CODE disorders will improve management of patients and advance our understanding of epithelial cells and other cells in the intestinal mucosa.
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影响因子：
30.8
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1007/s00428-017-2197-9
发表时间：
2018-01
期刊：
Virchows Archiv : an international journal of pathology
影响因子：
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通讯作者：
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DOI：
10.1016/j.jcmgh.2015.05.001
发表时间：
2015-07
影响因子：
7.2
作者：
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