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Congenital intestinal diarrhoeal diseases: A diagnostic and therapeutic challenge

https://doi.org/10.1016/j.bpg.2016.03.004Get rights and content

Abstract

Congenital diarrhoeal disorders are a heterogeneous group of inherited malabsorptive or secretory diseases typically appearing in the first weeks of life, which may be triggered by the introduction of distinct nutrients. However, they may also be unrecognised for a while and triggered by exogenous factors later on. In principle, they can be clinically classified as osmotic, secretory or inflammatory diarrhoea. In recent years the disease-causing molecular defects of these congenital disorders have been identified. According to the underlying pathophysiology they can be classified into four main groups:

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

4) Defects of the immune system affecting the intestine

Here, we describe the clinical presentation of congenital intestinal diarrhoeal diseases, the diagnostic work-up and specific treatment aspects.

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;

Conflict of interest

None.

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