Exudative diarrhea linked with extremely early-onset inflammatory bowel disease, osmotic or secretory diarrhea, and protein-losing enteropathy are all causes of early-onset refractory diarrhea. These illnesses include monogenic disorders, although a thorough genetic study has yet to be completed. Researchers created targeted gene panels that included all of the genes associated with early-onset diarrhea. This research included 108 patients from 15 different institutions. They gathered clinical information from all patients. Genetic testing was performed on 73 individuals with exudative diarrhea, 4 with osmotic or secretory diarrhea, and 8 with protein-losing enteropathy. A total of 15 of the 108 patients recruited were found to be monogenic. They found one patient with RELA, two with TNFAIP3, one with CTLA4, one with SLCO2A1, four with XIAP, three with IL10RA, one with HPS1, one with FOXP3, and one with CYBB gene mutations. From the gene panel for primary immunodeficiency syndromes, we also found 1 patient with NFKB2 mutations and 1 with TERT mutations. The patient’s persistent diarrhea was caused by heterozygous shortened RelA protein expression, and functional investigation indicated that the mutation impacted nuclear factor kappa B signaling. Genotypes were shown to be strongly related to clinical and pathological results in each patient.

They discovered that genes responsible for primary immunodeficiency disorders were commonly implicated in molecular pathogenesis in the individuals with varied monogenic diseases. For patients with early-onset refractory diarrhea, comprehensive genetic study proved beneficial for accurate molecular diagnosis, understanding of underlying pathophysiology, and selecting the best therapy.

Reference: https://journals.lww.com/jpgn/Abstract/2020/09000/Comprehensive_Targeted_Sequencing_Identifies.10.aspx