S4125 Alpha-Gal Syndrome: A Case Series Supporting the Need for Greater Clinical Recognition

Introduction: Unlike typical immunoglobulin E (IgE)-mediated food allergies triggered by proteins, alpha-gal syndrome (AGS) is a delayed hypersensitivity reaction to galactose-α-1,3-galactose (alpha-gal), a carbohydrate found in non-primate mammalian meat (e.g., beef, pork, lamb). This unique allergy arises due to a loss-of-function mutation in the α1,3-galactosyltransferase gene, rendering alpha-gal immunogenic in humans. Sensitization is often triggered by tick bites, leading to IgE-mediated responses several hours after meat consumption. Though potentially affecting hundreds of thousands in the U.S., AGS remains underdiagnosed and often misattributed due to its atypical presentation. Case Description: We present a case series of 3 patients of AGS with chronic non-specific gastrointestinal symptoms. A 27-year-old man presented with chronic non-specific gastrointestinal (GI) symptoms, including abdominal pain, alternating bowel habits, and nausea, along with fatigue, headache, and dizziness. His extensive GI and infectious workup, including computed tomography enteroclysis, stool studies, gastric emptying study, and esophagogastroduodenoscopy (EGD)/colonoscopy, were unrevealing. An elevated antinuclear antibody and persistent symptoms raised concern for an evolving autoimmune disease, ultimately revealing elevated beef-, lamb-, and pork-specific IgE and alpha-gal IgE (0.39 kU/L). Another 21-year-old with a strong family history of Crohn’s disease presented with nausea, episodic diarrhea, and food intolerance, particularly to red meat and dairy. Despite extensive workup, including a colonoscopy, EGD, celiac panel, and biopsies for inflammatory bowel disease and eosinophilic esophagitis, the diagnosis remained unclear. Diagnosed with AGS after elevated beef-, lamb-, and pork-specific IgE and alpha-gal IgE (12.4 kU/L) were found. A 59-year-old woman presented with cyclic nausea and vomiting. Initial labs and hepatobiliary iminodiacetic acid scan were unremarkable. EGD showed atrophic gastric mucosa and a 5 mm polyp consistent with carcinoid. Repeat EGD later in the year showed no recurrence of carcinoid or atrophic changes. Labs revealed a positive antiparietal cell antibody (1:160) and alpha-gal IgE of 50.90 kU/L. Dietary modification led to significant improvement in these patients. Discussion: AGS can present with non-specific GI symptoms after consumption of mammalian meat or related products. Clinicians should maintain a high index of suspicion and a low threshold for checking alpha-gal-specific IgE, especially in patients with tick exposure or intolerance to red meat. Early recognition and dietary modification can significantly improve symptoms.