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.
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.
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.
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.
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.
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.
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.
Furthermore, they support the notion that mislocalization of transporters, such as NHE3 substantially contributes to the reported sodium loss 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.
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.
The PFS of patients with EGFR mutation was 9.0 months and it in EGFR status unknown or wild type was 2.5 months .The most common toxicity included rash (54.1%) and diarrhea (31.1%).
EGFR mutation-positive Chinese patients (n = 52) treated with erlotinib were included in our study; the steady-state trough concentrations were assessed; and the occurrence and severity of skin rash and diarrhea after the onset of treatment with erlotinib were recorded.