P1483 - CODE Brown: A Case of a Novel Variant of a DGAT1 Mutation Causing DIAR7

Samantha Pendleton, DO¹, Mojdeh Mostafavi, MD², Timothy Menz, MD³, Wael Sayej, MD^3
1University of Massachusetts Chan Medical School - Baystate Medical Center, Springfield, MA; ²Massachusetts General Hospital, Harvard Medical School, Boston, MA; ³Baystate Medical Center, Springfield, MA

Introduction: While occasional diarrhea is exceedingly common within the pediatric population and often benign, persistent diarrhea is more frequently pathologic in nature and may represent a rare diagnosis known as Congenital Diarrheas and Enteropathies (CODEs). Several mutations in diacylglycerol O-acyltransferase 1 (DGAT-1), an enzyme involved in triglyceride synthesis, have been shown to cause CODEs. It is hypothesized that such mutations in DGAT-1 result in disruption of the intestinal barrier leading to impaired lipid digestion and malabsorption, referred to as Diarrhea Type 7 (DIAR7).

Case Description/Methods: We present a case of an initially 7-month-old male infant who presented to our hospital from Pakistan for workup of chronic diarrhea and failure to thrive (FTT). He had gained only ~1kg since birth despite trialing of several formulas via NG as well as total parenteral nutrition. Upon arrival to our hospital, he required resuscitation in the pediatric ICU and underwent a largely negative workup including normal stool reducing substances, fecal calprotectin, negative stool ova/parasite, and a grossly and histologically normal EGD/sigmoidoscopy. His fecal elastase was low, and PCR did return positive for enteropathogenic E. coli, for which he received a 3-day course of azithromycin. He began to gain weight slowly after switching to a carbohydrate-free formula with placement of a G tube and reinitiation of TPN. Five weeks into admission the congenital diarrhea panel returned positive with a homozygous variant in the DGAT1 gene resulting in a partial deletion from Exon 8 (c676+9_725del). This variant had not been previously reported in the literature of individuals affected by DGAT1-related conditions but was identified as being likely pathogenic. As such, this mutation is believed to be responsible for his clinical presentation of DIAR7. He was switched to a low-fat, high-MCT milk-protein-based formula and continued intralipids with a weight gain of 3.5kg at discharge, 3 months after admission. Patient continued to improve as an outpatient, gaining an additional 4kg. His G-tube has since been removed with plan to wean off intralipids.

Discussion: This case identifies a novel DGAT1 variant resulting in DIAR7, contributing to the growing knowledge in identification and treatment of CODEs. While diarrhea remains a common complaint in pediatric patients, it is important to consider rare causes such as CODEs when chronic diarrhea leads to FTT.


Disclosures:


Samantha Pendleton, DO¹, Mojdeh Mostafavi, MD², Timothy Menz, MD³, Wael Sayej, MD³. P1483 - CODE Brown: A Case of a Novel Variant of a DGAT1 Mutation Causing DIAR7, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.