4Congenital intestinal diarrhoeal diseases: A diagnostic and therapeutic challenge
Introduction
Congenital diarrhoeal disorders (CDD) are rare and can be classified into secretory, inflammatory, or malabsorptive forms. Malabsorptive or osmotic diarrhoea improves with fasting, whereas secretory and inflammatory forms are not influenced. In addition, malabsorptive disorders can be grouped according to the response to dietary challenges into either selective or generalized impairment of nutritional transport (Fig. 1). Clinically, they may present either solely with diarrhoea or together with other symptoms, or as a systemic disease. Histological investigations may reveal abnormalities of the crypt-villous structure, enterocyte distribution, and morphology or inflammatory activity and may discriminate between some disorders (Fig. 2). In addition, molecular analysis elucidated disease-causing genes and provide an advantageous diagnostic approach in identifying patients with suspected CDD (Table 1, Table 2, Table 3, Table 4) [1]. We adopted the classification of Canani et al. into four CDD groups based on the mechanism involved in the pathophysiology (Fig. 3, Fig. 4): 1.) Defects of digestion, absorption and transport of nutrients or electrolytes; 2.) Defects of absorptive enterocyte differentiation or polarisation; 3.) Defects of the enteroendocrine cells; and 4.) Defects of the immune system [1].
Section snippets
Defects of digestion, absorption and transport of nutrients or electrolytes
These diseases typically appear early after birth with severe diarrhoea with subsequent dehydration and weight loss. History of prenatal polyhydramnios or presence of liquid filled intestinal loops already indicating disturbed electrolyte transport. Small mucosal biopsy specimens do not show any morphological injury. A diagnostic algorithm is shown in Fig. 5. The defects are grouped into defects of the brush border membrane, membrane carriers, pancreatic enzymes, lipid transport and metabolism,
Defects of the immune system affecting the intestine
Chronic diarrhoea, malabsorption, and inflammatory bowel disease with early onset are indicative for immunodeficiency disorders [67]. The gut is the largest lymphoid organ and thereby it is not surprising that patients with primary immunodeficiency develop immune-related gastrointestinal diarrhoeal disorders via autoimmune, infectious, and inflammatory reactions [67], [68]. Diagnosis is based on history of serious or atypical infections, immunological investigations, and molecular genetics;
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2021, Pediatrics and NeonatologyCitation Excerpt :Mutations in the proteins involved in fat transport or metabolism cause failure in the absorption or transport of the fats such as abetalipoproteinemia (MTTP) or chylomicron retention disease (SAR1B). Apart from these disorders, mutations of approximately 20 disorders associated with the defect in DATN have been defined up to date.1,3,14,15 Recently, a novel genetic entity caused by mutations in DGAT1 which is involved in cellular triglyceride formation has been defined characterized by electrolyte transport-related diarrhea, vomiting and PLE induced by enteral intake of lipids.16,17
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2020, Clinics in PerinatologyCitation Excerpt :There are myriad groups of immunologic disorder and they are summarized in Table 4. The approach to diagnose a case with neonatal diarrhea is illustrated in Fig. 2 that includes 4 algorithms.5,17,20,44 The first algorithm presents the key points to identify whether the diarrhea is congenital or acquired and whether it is osmotic or secretory diarrhea (see Fig. 2A).
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2018, European Journal of Medical GeneticsCitation Excerpt :The variants were first filtered with the in-house “VarAFT” system (http://varaft.eu) focusing on the 29 genes linked to congenital diarrheal syndrome to date (Table 1 SI. ( Canani et al., 2015; Posovszky, 2016). Using frequency below 0.01 on Exac Browser (http://exac.broadinstitute.org/) only one candidate gene remained: TTC7A.