Familial GUCY2C diarrhea syndrome (FGDS) is an autosomal dominant disorder found in 32 members of a Norwegian family and caused by a heterozygous missense resulting in chronic diarrhea. The study aimed to investigate any abnormality in the enteroendocrine cells in the terminal ileum of the affected family members. Terminal ileal biopsies from 11 FGDS patients and 14 healthy controls (HC) were stained using immunohistochemistry for chromogranin A, serotonin, and peptide YY (PYY) and quantified using computerized image analyses. Global gene expression of PYY in the ileal biopsies was performed. The densities of PYY-immunoreactive cells in the terminal ileum (mean ± SEM values) of HC and FGDS patients were 48.1 ± 4.8 and 25.3 ± 5.8 cells/mm2, respectively, p = 0.01. No significant changes were found in the densities of CgA and serotonin immunoreactive cells between the two groups. The gene expression of PYY was significantly lower in family members with FGDS than in HC (p = 0.001). In conclusion, lower expression of PYY gene and PYY-immunoreactive cell density is found in FGDS patients than healthy controls. PYY acts as an anti-diarrheal agent by inhibiting the agonists of cyclic adenosine monophosphate (cAMP). Both cyclic guanosine monophosphate (cGMP) and cAMP activate the cystic fibrosis transmembrane regulator and may cause diarrhea.
Mazzawi et al. (Sun,) studied this question.