Awosika A, Balaji P. Misdiagnosis of alpha-gal syndrome as non-celiac gluten sensitivity or lactose intolerance: A diagnostic blind spot for clinicians. World J Gastroenterol 2026; 32(3): 116350 [DOI: 10.3748/wjg.v32.i3.116350]
Corresponding Author of This Article
Ayoola Awosika, MD, Department of Family Medicine, University of Illinois College of Medicine Peoria, 1 Illini Drive, Bloomington, IL 61601, United States. ayoolaawosika@yahoo.com
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Medicine, General & Internal
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jan 21, 2026 (publication date) through Jan 18, 2026
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World Journal of Gastroenterology
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1007-9327
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Awosika A, Balaji P. Misdiagnosis of alpha-gal syndrome as non-celiac gluten sensitivity or lactose intolerance: A diagnostic blind spot for clinicians. World J Gastroenterol 2026; 32(3): 116350 [DOI: 10.3748/wjg.v32.i3.116350]
World J Gastroenterol. Jan 21, 2026; 32(3): 116350 Published online Jan 21, 2026. doi: 10.3748/wjg.v32.i3.116350
Misdiagnosis of alpha-gal syndrome as non-celiac gluten sensitivity or lactose intolerance: A diagnostic blind spot for clinicians
Ayoola Awosika, Prithvi Balaji
Ayoola Awosika, Prithvi Balaji, Department of Family Medicine, University of Illinois College of Medicine Peoria, Bloomington, IL 61601, United States
Author contributions: Awosika A was involved in conceptualization, methodology, synthesis, writing first and review final draft; Balaji P was involved in methodology, synthesis, writing second draft, editing and review final draft.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ayoola Awosika, MD, Department of Family Medicine, University of Illinois College of Medicine Peoria, 1 Illini Drive, Bloomington, IL 61601, United States. ayoolaawosika@yahoo.com
Received: November 10, 2025 Revised: November 18, 2025 Accepted: December 8, 2025 Published online: January 21, 2026 Processing time: 68 Days and 14.6 Hours
Abstract
Alpha-gal syndrome (AGS), an emerging tick-borne carbohydrate hypersensitivity, has gained increasing recognition for its atypical presentation and delayed food-related allergic reactions. While urticaria and anaphylaxis dominate the clinical narrative, gastrointestinal (GI) manifestations-including abdominal pain, diarrhea, bloating, and cramping-are common and often underrecognized. These nonspecific GI symptoms create significant diagnostic overlap with prevalent functional and food-related disorders such as non-celiac gluten sensitivity (NCGS) and lactose intolerance. Consequently, many patients with AGS undergo unnecessary dietary restrictions, prolonged symptom burden, or misdirected therapies before an accurate diagnosis is established. The knowledge gap lies in the limited awareness of AGS as a differential diagnosis for food-related GI complaints, especially in regions endemic to tick exposure. Unlike gluten or lactose intolerance, AGS reactions are characterized by a unique delayed onset (2-6 hours postprandially) and a distinct immunologic mechanism mediated by IgE to galactose-α-1,3-galactose. However, clinicians rarely consider AGS when evaluating chronic, unexplained food-triggered symptoms, perpetuating diagnostic blind spots. Current guidelines for evaluating NCGS and lactose intolerance seldom incorporate testing for alpha-gal IgE, despite growing evidence that a subset of misdiagnosed patients may in fact harbor AGS. Clinically, this misclassification carries significant consequences: Patients may continue mammalian food exposure with risk of escalating allergic reactions, including life-threatening anaphylaxis, while adhering to unnecessary or ineffective gluten-free or lactose-free diets. Raising awareness, integrating alpha-gal IgE testing into gastroenterology workups, and refining diagnostic algorithms are urgently needed. Addressing this blind spot has the potential to reduce morbidity, improve diagnostic accuracy, and optimize individualized patient care.
Core Tip: Integrating alpha-gal syndrome into the differential diagnosis of unexplained postprandial gastrointestinal symptoms - particularly in individuals from or with travel to tick-endemic areas - is imperative. Awareness of the unique etiologic and immunologic underpinnings of alpha-gal syndrome provides clinicians with a framework to recognize atypical presentations. Concerted efforts are needed to refine diagnostic algorithms, including the judicious use of serum α-gal-specific IgE testing in appropriate clinical contexts, and to develop multidisciplinary pathways linking gastroenterology, allergy/immunology and nutrition.
