Evaluation of the Effect of a Low-FODMAP Diet on Gastrointestinal Symptoms and Inflammatory Markers in Fabry Patients

Fabry disease is a rare X-linked lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A, leading to the progressive accumulation of glycosphingolipids, particularly globotriaosylceramide (Gb3), in various tissues and organs. Gastrointestinal manifestations, including abdominal pain, bloating, nausea, diarrhea, and constipation, are common and can negatively affect nutritional status and quality of life. Although enzyme replacement therapy is an established treatment for Fabry disease, gastrointestinal symptoms may persist despite treatment.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are short-chain carbohydrates that may contribute to gastrointestinal symptoms by increasing intestinal water content and colonic gas production. A low-FODMAP diet has demonstrated beneficial effects on gastrointestinal symptoms in patients with irritable bowel syndrome, and preliminary evidence suggests potential benefits in patients with Fabry disease. However, its effects on inflammatory biomarkers and nutritional parameters in this patient population remain insufficiently investigated.

This randomized controlled study aims to evaluate the effects of a six-week low-FODMAP diet on gastrointestinal symptoms, inflammatory biomarkers, nutritional status, and quality of life in pediatric and adult patients with Fabry disease.

The study will include 30 patients with genetically or laboratory-confirmed Fabry disease who are followed at Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Division of Pediatric Nutrition and Metabolism. Participants will be randomly assigned to one of two groups:

Intervention group: Participants will receive an individualized low-FODMAP diet designed to meet their age-, sex-, and energy-specific nutritional requirements. Foods high in fermentable carbohydrates, including excess fructose, lactose, fructans, galacto-oligosaccharides, and polyols, will be restricted and replaced with suitable low-FODMAP alternatives. Individualized meal plans will be provided, and dietary adherence will be monitored through daily online follow-up sessions throughout the six-week intervention.

Control group: Participants will continue their habitual, unrestricted diet without a specific dietary intervention during the six-week study period.

At baseline and after six weeks, participants will undergo comprehensive nutritional, anthropometric, biochemical, and clinical assessments. Anthropometric measurements will include body weight, height, skinfold thickness, mid-upper arm circumference, and body composition assessed by bioelectrical impedance analysis. Dietary intake will be evaluated using three-day food records and food frequency assessments.

Gastrointestinal symptoms will be assessed using the Gastrointestinal Symptom Rating Scale (GSRS), while stool characteristics will be evaluated using the Bristol Stool Form Scale. Health-related quality of life will be assessed using the 36-Item Short Form Health Survey (SF-36).

Biochemical assessments will include hematological and nutritional parameters, lyso-globotriaosylceramide (Lyso-Gb3), and inflammatory biomarkers, including neopterin, biopterin, tryptophan, and kynurenine.

Changes in gastrointestinal symptoms, inflammatory biomarkers, nutritional parameters, and quality of life will be compared between the intervention and control groups. The study will also investigate potential relationships between dietary adherence, gastrointestinal symptom improvement, inflammatory biomarkers, and quality of life.

The findings are expected to contribute to the understanding of the potential role of individualized dietary interventions in the management of gastrointestinal manifestations and inflammation in Fabry disease.