The consumption of wheat-based products is high in most West- ern countries (e.g. Europe, United States) and is increasing in East- ern countries as a consequence of a shift toward a Western lifestyle. Historically, Wheat-Related Disorders (WRD) referred only to wheat allergy and celiac disease. In recent years, a growing number of sub- jects worldwide have reported intestinal and extraintestinal symp- toms, without the diagnostic features of celiac disease or wheat al- lergy. In these subjects, symptoms of a wheat-related disorder may originate from non-celiac gluten sensitivity, the non-gluten antibody target protein serpins, purinins, α-amylase/protease inhibitors, glob- ulins, farinins, wheat exorphin sensitivity, wheat germ agglutinin sen- sitivity, wheat amylase-trypsin inhibitor sensitivity, and/or FODMAP (fermentable oligo-, di-, mono- saccharides and polyols) sensitivity. This article reviews the pertinent literature and presents three pediat- ric cases of wheat-related disorders that present with varied clinical presentations: liver failure, type 1 diabetes mellitus and a conjuncti- val tumor believed to be Kaposi’s sarcoma. All conditions responded rapidly to a wheat-free diet. A wheat-related disorder (with or without
celiac disease) may affect any organ or system including cardio- vascular disease, neurological diseases, connective tissue diseas- es, allergies, in ammatory bowel disease, nephritis and others. While there is increasing awareness that wheat-related disorders can manifest with extra-intestinal symptoms, clinicians still rely too heavily on the presence of gastrointestinal symptoms to suspect a wheat-related disorder. These three cases showed wheat-related pathogenesis affecting diverse organs, such as the liver, pancre- as, or eye, without marked gastrointestinal symptoms. Therefore, in patients with unexplained symptoms, who do not improve with stan- dard therapies, it may be prudent to screen for serological indicators of a WRD. Clinical awareness of the diversity of presentations of a WRD may lead to earlier suspicion, investigation and a reduction in co-morbidity.