Abstract Background Diacylglycerol O-acyltransferase 1 (DGAT1) deficiency is a rare autosomal recessive disorder that disrupts intestinal triglyceride metabolism, leading to congenital diarrhea and enteropathy. This study aimed to characterize the phenotypic and genotypic spectrum of DGAT1 deficiency, evaluate the genotype–phenotype correlations, and assess outcomes following nutritional interventions. Methods We retrospectively analyzed 12 pediatric patients with DGAT1 deficiency diagnosed between 2016 and 2025. Clinical data, genetic profiles, management, and outcomes were collected. Whole-exome sequencing with Sanger validation was performed, and pathogenicity was classified according to the American College of Medical Genetics and Genomics criteria. A systematic review identified 58 previously reported patients. Kaplan–Meier survival analysis evaluated survival, and Fisher’s exact test assessed associations between specific genetic variants and treatment responses. Results Among 70 patients, 84.3% presented in the neonatal period. The most frequent symptoms were diarrhea (90.0%), vomiting (81.4%), and failure to thrive (84.3%), with hypoalbuminemia observed in 87.1%. Splice-site variants were most prevalent (37.2%) with distinct ethnic distributions. Homozygous variants, especially missense mutations, were associated with more severe manifestations and poorer survival compared with compound heterozygous or splice-site variants (P = 0.0203). All nine deaths occurred in patients under 2 years of age. A fat-restricted diet significantly improved survival, while recurrent infections were linked to poor outcomes (P < 0.0001). Overall, 80.5% of patients achieved sustained clinical improvement with dietary therapy. Furthermore, the specific genetic variant c.629_631del was identified as a predictor of poor dietary response (P = 0.0497). Conclusions DGAT1 deficiency typically presents with early-onset refractory diarrhea and nutritional complications. Early genetic testing and prompt initiation of a fat-restricted diet within the first 2 years of life markedly improve survival and long-term outcomes.
Abstract Background While substantial evidence supports a protective effect of aspirin against colorectal polyps and cancer, the evidence for non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) remains limited. We studied the association between the use of NA-NSAIDs and the detection of colorectal polyps and cancer among screening participants. Methods We selected participants in the Bowel Cancer Screening trial in Norway—a randomized trial comparing once-only sigmoidoscopy and the biennial faecal immunochemical test (FIT). Using multivariable logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between NA-NSAID use in the 4 years before the screening invitation and detection of colorectal cancer (CRC), adenomas, advanced adenomas, and advanced serrated polyps. Long-term use was defined as ≥2 years of use. Results Of 64,889 participants (24,159 sigmoidoscopy, 40,730 FIT), 35,867 (55.3%) were NA-NSAID users, 314 (0.5%) had CRC, 6,208 (9.6%) had adenomas, and 659 (1.0%) had advanced serrated polyps. NA-NSAID users had lower odds of CRC (OR 0.80; 95% CI 0.64–1.00), adenomas (OR 0.94; 95% CI 0.89–1.00), and advanced adenomas (OR 0.87; 95% CI 0.80–0.95) than those with no NA-NSAID prescription. For non-selective NA-NSAIDs, the results were similar to those for any NA-NSAIDs (CRC: OR 0.79, 95% CI 0.63–0.99; adenomas: OR 0.93, 95% CI 0.88–0.99; advanced adenomas: OR 0.87, 95% CI 0.79–0.95). COX2-selective NA-NSAIDs were not associated with CRC or adenomas. Among the long-term NA-NSAIDs users, the ORs were 0.59 (95% CI 0.27–1.26) for CRC, 0.65 (95% CI 0.54–0.79) for adenomas, and 0.59 (95% CI 0.44–0.80) for advanced adenomas. No association was observed between any NA-NSAID use and advanced serrated polyps. The results were consistent across trial arms and sexes. Conclusion Our findings suggest that use of NA-NSAIDs, in particular non-selective NA-NSAIDs, might be associated with a reduced risk of adenomas and CRC, but not advanced serrated polyps.
