A patient presenting at our institution at 7 weeks of life with failure to thrive and diarrhea was found by whole-exome sequencing to have a homozygous DGAT1 truncation mutation.
Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA.
Our findings add to the growing recognition of DGAT1 deficiency as a cause of congenital diarrhea with protein-losing enteropathy and indicate that <i>DGAT1</i> mutations result in a spectrum of diseases.
The precise cause of diarrhea is unknown, but we speculate that it relates to abnormal fat absorption and buildup of DGAT substrates in the intestinal mucosa.
Because GUCY2C heterozygous and homozygous mutant mice are resistant to E. coli STa enterotoxin-induced diarrhea, it is plausible that GUCY2C mutations in the desert-dwelling Bedouin kindred are of selective advantage.
MYO5B deficiency appears to impair targeting of BSEP to the canalicular membrane with hampered bile acid excretion, resulting in a spectrum of cholestasis without diarrhea.(Hepatology 2017;65:1655-1669).
Enterotoxigenic <i>Escherichia coli</i> (ETEC) is a leading cause of childhood death from diarrhea and the leading cause of Traveler's diarrhea.<i>E. coli</i> heat-stable enterotoxin (ST) is a major virulence factor of ETEC and inhibits the brush border Na/H exchanger NHE3 in producing diarrhea.
Reduced NHE3 expression or function has been implicated in the pathogenesis of diarrhea associated with inflammatory bowel disease (IBD) or enteric infections.
Na<sup>+</sup>/H<sup>+</sup> exchanger-3 (NHE3) is crucial for intestinal Na<sup>+</sup> absorption, and its reduction has been implicated in infectious and inflammatory bowel diseases (IBD)-associated diarrhea.
Studies have shown that a decrease in both NHE3 (Na<sup>+</sup>/H<sup>+</sup> exchanger) and DRA (downregulated in adenoma, Cl<sup>-</sup>/[Formula: see text] exchanger), resulting in decreased electrolyte absorption, is implicated in infectious and inflammatory diarrhea.
Furthermore, they support the notion that mislocalization of transporters, such as NHE3 substantially contributes to the reported sodium loss diarrhea.
It was shown that the expression levels of NHE3 and AQP4 were significantly increased in the diarrhoea mice treated with berberine compared with the untreated diarrhoea mice.
In SMP30 deficient mice, colitis was significantly exacerbated as demonstrated by increased mortality (p = 0.001), body weight loss (p = 0.0105 at day 8), rectal bleeding (p = 0.0047 at day 8) and diarrhea (p = 0.0030 at day 8), histological scores (ulcers, p = 0.0002; edema, p = 0.0125; leukocyte infiltration, p = 0.0016) and productions of pro-inflammatory cytokines (IL-1α, p = 0.0452; IL-6, p = 0.0074; G-CSF, p = 0.0036).
Other fecal cytokines (IL-1beta and IL-1ra) were found in increased concentrations (P < 0.05 when at least one EAEC virulence factor was present compared with the concentrations when EAEC negative for multiple virulence factors was found in patients with diarrhea.
Intestinal epithelial apical membrane Cl-/HCO3- exchanger DRA (downregulated in adenoma, SLC26A3) has emerged as an important therapeutic target for diarrhea, emphasizing the potential therapeutic role of agents that upregulate DRA.
Congenital chloride losing diarrhea (CCLD) is a rare type of chronic watery diarrhea due to mutations in SLC26A3 gene leading to defective chloride-bicarbonate exchanges with the resultant loss of chloride and retention of bicarbonate.We aim to define pediatric Saudi CCLD patients' characteristics to achieve prompt diagnosis, management, follow up with good quality of life, and prevention of complications in these patients.We carried retrospective data review of demographic, clinical, laboratory, radiographic, and outcome of all pediatric patients fulfilling the criteria of CCLD over 10 years from 2004 to 2014 from a single center in Taif region, Saudi Arabia.Forty-nine patients fulfilled the criteria of CCLD from 21 families with more than one affected patient in the same family in 90% of them and positive consanguinity in 91% of the cohort.