Faculty Collaboration Database

Clinical course and therapeutic trial for a case of congenital secretory diarrhea due to novel GUCY2C variant. Am J Med Genet A 2024 Apr;194(4):e63489

Date

12/07/2023

Pubmed ID

38058249

DOI

10.1002/ajmg.a.63489

Scopus ID

2-s2.0-85178961963 (requires institutional sign-in at Scopus site)

Abstract

Chronic diarrhea presents a significant challenge for managing nutritional and electrolyte deficiencies, especially in children, given the higher stakes of impacting growth and developmental consequence. Congenital secretory diarrhea (CSD) compounds this further, particularly in the case of the activating variants of the guanylate-cyclase 2C (GUCY2C) gene. GUCY2C encodes for the guanylate-cyclase 2C (GC-C) receptor that activates the downstream cystic fibrosis transmembrane receptor (CFTR) that primarily drives the severity of diarrhea with an unclear extent of influence on other intestinal channels. Thus far, management for CSD primarily consists of mitigating nutritional, electrolyte, and volume deficiencies with no known pathophysiology-driven treatments. For activating variants of GUCY2C, experimental compounds have shown efficacy in vitro for direct inhibition of GC-C but are not currently available for clinical use. However, Crofelemer, a CFTR inhibitory modulator with negligible systemic absorption, can theoretically help to treat this type of CSD. Herein, we describe and characterize the clinical course of a premature male infant with a de novo missense variant of GUCY2C not previously reported and highly consistent with CSD. With multi-disciplinary family-directed decision-making, a treatment for CSD was evaluated for the first time to our knowledge with Crofelemer.

Author List

Scott W, Wong IGY, Cramer J, Horton D, Basel D, Teng RJ, Muriello M, Elkadri A

Authors

Donald Basel MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Jesse L. Cramer PharmD Adjunct Assistant Professor in the School of Pharmacy Administration department at Medical College of Wisconsin
Abdul Aziz Elkadri MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Michael Muriello MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Ru-Jeng Teng MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Child
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Diarrhea
Disease Progression
Electrolytes
Humans
Intestines
Male
Receptors, Enterotoxin