Phenotypic and genotypic characterization of DGAT1 deficiency in pediatric patients with congenital diarrhea and enteropathy

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.