Novel variant and enteroendocrine hormone deficiency in a patient with proline and glutamate-rich protein with a coiled coil domain 1 (PERCC1) associated enteropathy: New diagnostic and therapeutic insights

Proline and glutamate-rich protein with a coiled coil domain 1 (PERCC1)-associated enteropathy is a rare monogenic congenital diarrhea due to defective enteroendocrine cells (EECs). We describe a 6-year-old female with intestinal failure since birth. Biopsies demonstrated normal appearing gastric mucosa on hematoxylin and eosin stains. Commercial whole-exome sequencing did not reveal clinically relevant variants. Subsequent testing, prompted by undetectable serum Gastrin, identified compound heterozygous variants in PERCC1: c.390 C > G (Y130X) and a novel c.492del (S164RfsX33) variant. Hormonal profiling showed low endogenous glucagon-like peptide (GLP)-1 and -2 levels, pre and postprandial. Immunohistochemistry showed a markedly reduced density of Gastrin containing G-cells and preserved EEC. At 5.5 years, endogenous GLP-2 deficiency supported off-label Teduglutide therapy. Baseline Parenteral Nutrition Dependency Index (PNDI) was 67%; after 16 months, PNDI decreased to 35%, with improved stool output and appetite. Congenital diarrhea with low serum levels of Gastrin, GLP-1, and -2 and abnormal G-cell staining should prompt targeted genetic analysis for PERCC1 with whole genome sequencing. Timely diagnosis enables Teduglutide therapy and parenteral nutrition weaning.