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

Abstract 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.