Case Report: DGAT1 deficiency in three infants including a novel missense variant: structural insights and comparison with reported cases

Introduction DGAT1 deficiency is a rare cause of congenital diarrhea and protein-losing enteropathy, with only 39 reported cases and limited characterization of missense variants. This study integrates molecular interpretation with clinical data to refine genotype–phenotype correlations. Case description Three Palestinian infants with DGAT1 deficiency were analyzed, and a structured literature search was conducted. The diagnosis was established by whole-exome sequencing, with confirmatory Sanger sequencing. A novel variant underwent segregation testing, conservation assessment, and three-dimensional protein modeling using cryo-electron microscopy structures. All patients presented with congenital diarrhea, hypoalbuminemia, and severe growth faltering. Two known loss-of-function variants (c.1183C>T; p.Arg395Ter and c.895-1G>A) and one novel homozygous missense variant (c.820C>T; p.Arg274Trp) were identified. Structural modeling localized the residue to the substrate tunnel, where substitution of arginine with tryptophan is predicted to disrupt acyl-CoA entry into the catalytic chamber. Literature comparison suggests a partial residual function consistent with later presentation. All patients improved with low-fat, amino acid–based nutrition. Conclusion These findings expand the DGAT1 mutational spectrum and support the potential value of structure-informed analysis in the interpretation of rare missense variants, while highlighting the importance of early recognition and targeted nutritional therapy.