Advancing Management of Pediatric Celiac Disease: Genetics, Diagnosis, and Health Trajectories

Aim: The purpose of this review isto investigate the complexity of celiac disease (CD) in the pediatric population, specifically the genetics, immunology, microbiology, nutrition, association of comorbidities such as type 1 diabetes mellitus (T1DM), neurodevelopmental disorders, and congenital hypothyroidism, as well as promising new diagnostics and therapeutics, including a gluten-free diet (GFD).  Methods: A thorough investigative analysis was conducted with 22 peer-reviewed journal publications from 1987 to 2024. The review papers cited original research, reviews, and clinical papers from PubMed and ScienceDirect. The analysis and review papers reported key themes of: (1) genetic susceptibility, (2) gut microbiome, (3) comorbidities and complications in children, (4) diagnostics, and (5) therapeutics, including GFD and pharmacological therapy.  Results: Genetic predisposition is a significant factor of CD, especially the HLA-DQ2 and DQ8 alleles(Sollid et al., 2021; Liu et al., 2020), although they are not the only loci that are having non-HLA loci having significance with CD. Patients with CD are at significantly higher risk to develop co- existing autoimmune and endocrine disorders such as T1DM and congenital hypothyroidism (Stagi et al., 2011; Lewandowska et al., 2018). Additionally, studies indicated a connection between CD and neurodevelopmental disorders, including altered urine peptide profiles, and vitamin D function (Bojović et al., 2019). Gut microbiome is more likely a risk factor rather than a consequence in CD, with dysbiosis impairing gluten immune tolerance (Cukrowska et al., 2021; Zhang et al., 2023). Nutritional deficiencies resulting from malabsorption and on dietary restrictions may create growth delays, micronutrient deficiencies, and mental health issues. (Fritsch et al., 2010; Lifshitz & Tarim, 1993). The GFD is the current standard of care, however a strict GFD continues to be less than optimal in more pediatric cases. Promising new pharmacological therapy, and revolutionary enzyme therapy, are underway (Leffler et al., 2022). Promising diagnostics are based on high- throughput testing; specifically, new microbiome profiling in the early and ongoing diagnosis (Lebwohl et al., 2020; Green et al., 2020). Further, and continuous, development of digital health technologies aimed toward optimizing care and access for children with CD. Conclusion: Celiac disease in children represents not only a gastrointestinal disease but a systemic condition with broad implications for immunology, metabolism, and even psychosocial influences. Genetic and serological screening in the early stages of diagnosis is important for determining CD, with microbiome aware strategies, especially for at-risk groups. The GFD is and will continue to be important, but personalized medicine, including digital health and targeted pharmacotherapy, provides the future direction toward a more comprehensive and sustainable management strategy in the pediatric population