Variants in DGAT1 causing enteropathy: a case report and review of the literature

Abstract

Background: Diacylglycerolacyltransferase 1 (DGAT1) is an enzyme that catalyzes the final step of triglyceride synthesis and genetic variants have been described in association with congenital diarrhea.

Methods: We present a patient with a novel variant in the DGAT1 gene and a review of previously published cases. A search was conducted in PubMed, Cochrane Library and Embase until December 2020 and 22 cases of children diagnosed with variants in DGAT1 and gastrointestinal disease were identified from 8 articles. Data on patient characteristics, clinical presentation, diagnostic findings and treatment were extracted and analyzed.

Case description: Our patient presented with failure to thrive, vomiting and diarrhea and was diagnosed with protein-losing enteropathy. The novel homozygous variant c.469-2A>G in DGAT1 was found and after starting with parenteral nutrition and a fat-free diet, she showed a favourable evolution with dramatic improvement of growth.

Results: A vast majority of patients presented with symptoms of failure to thrive, vomiting and diarrhea within the first three months of life but not necessarily at birth. Parenteral nutrition was required in 78.2% of cases and 61.1% of them weaned off. At follow-up, 73.7% were receiving a fat-restricted diet. Mortality was 17.4%.

Discussion: DGAT1 deficiency is a rare but severe disorder, that will likely be encountered more often in the future as DGAT1 is added to screening panels for congenital diarrhea. Key to the treatment is restriction of enteral fat with appropriate parenteral supplementation, but more detailed information on nutritional management strategies and their effects on clinical outcome is needed.