Unraveling the Hidden Burden of Gastrointestinal and Nutritional Challenges in Children with Fabry Disease: A Systematic Review with Meta-Analysis.

BACKGROUND/OBJECTIVES: Fabry Disease (FD) is a multisystem X-linked lysosomal storage disorder that often manifests with nonspecific gastrointestinal (GI) symptoms, such as abdominal pain, diarrhea, and constipation. These symptoms may appear early in childhood, severely impacting quality of life and delaying diagnosis, and may be linked to nutritional challenges. This systematic review aims to evaluate the prevalence, characteristics, clinical relevance, and nutritional aspects of GI manifestations in pediatric FD patients to aid in early recognition and improve outcomes.

METHODS

A systematic literature search with meta-analysis adhering to PRISMA and MOOSE guidelines was conducted across PubMed, Web of Science, and Google Scholar from inception to November 2024 using fixed inclusion and exclusion criteria. Data were extracted by two reviewers independently. Disagreements were resolved by consensus; a third reviewer was consulted, when necessary. Pooled analysis was performed by a random-effects model; heterogeneity was assessed using the I method. A quality assessment appraisal of the studies was carried out using the ROBINS-I tool.

RESULTS

The review encompassed 18 studies involving 736 pediatric patients. The evaluation of the pooled prevalence of GI symptoms in FD patients was 53% (95% CI 38-68%, I 90%), with abdominal pain being the most frequent (pooled prevalence of 46% (95% CI 33-60%, I 86%)). Symptoms often presented early, with a summarized standardized mean difference between the mean age of symptom onset and the mean age at FD diagnosis of 2.07 years (95% CI of 0.56-3.57, I 42%, < 0.01). Nutritional issues, including reduced food intake and potential malabsorption, were reported in cases with severe GI symptoms, contributing to growth impairments.

CONCLUSIONS

GI symptoms frequently constitute the earliest clinical manifestation of FD in children. Their nonspecific nature underscores the importance of heightened clinical suspicion for timely diagnosis. Early intervention, including enzyme replacement therapy and tailored nutritional strategies, can alleviate symptoms, improve quality of life, and prevent disease progression. Multidisciplinary approaches are essential to optimize patient outcomes and further research into the pathophysiology and management of GI symptoms in FD is warranted.