Clinical and Immunological Prognostic Factors With Novel Variants in a Large Cohort of Diacylglycerol Acyltransferase 1 Deficiency Publisher Pubmed



Yorgun Altunbas M^{1, 2, 3} ; Kogler H⁴ ; Abolhassani H^{5, 6} ; Akkus E⁷ ; Basturk A⁸ ; Akkelle E⁹ ; Sayar E¹⁰ ; Polat E¹¹ ; Kara A¹² ; Can S^{1, 2, 3} ; Frohne A¹³ ; Segarraroca A¹³ ; Jimenezheredia R^{13, 14, 15} ; Babayeva R^{1, 2, 3} Show All Authors
Source: Journal of Allergy and Clinical Immunology: In Practice Published:2025

Abstract

Background: Biallelic variants in diacylglycerol acyltransferase 1 (DGAT1) genegene have been implicated congenital diarrhea and protein-losing enteropathy. Insights into the immunopathologic features of this ultrarare disorder remain scarce, with only one cohort published to date. Objective: To delineate the clinical presentations, laboratory and immunologic profiles, and therapeutic responses associated with DGAT1 deficiency and identify prognostic indicators that affect survival rates. Methods: In this multicenter retrospective analysis of a comprehensive cohort of nine patients carrying seven novel variants, each displaying distinct phenotypic features, we recorded clinical, immunologic, and laboratory data of patients and evaluated the impact of various factors on prognosis. Results: A total of 67% of patients (n = 6) exhibited symptoms during the first month of life, whereas one demonstrated symptom onset after 6 months. Moreover, 78% of patients (n = 7) presented with diarrhea, all of whom all had vomiting, failure to thrive, hypoalbuminemia, and hypogammaglobulinemia as the advent of protein-losing enteropathy. Patients with reduced CD4+ T-cell frequency (n = 2) exhibited severe infections with unexpected bacteria during the follow-up. Despite immunoglobulin replacement therapy, 45% of patients (n = 4) died of infective complications. A decreased CD4+/CD8+ T-cell ratio was observed in all deceased patients whose colon biopsy samples showed marked inflammation or apoptosis. Early fat-restricted nutrition extended survival, whereas early symptom onset, recurrent severe infections, and a reduced CD4+/CD8+ T-cell ratio were associated with less favorable outcomes. Conclusions: Our findings advocate early fat restriction as a critical therapeutic strategy. Given the heightened risk of severe infections, antibiotic prophylaxis can be recommended in addition to immunoglobulin replacement therapy for DGAT1-deficient patients exhibiting lymphopenia or diminished CD4+ T cells. © 2025 American Academy of Allergy, Asthma & Immunology