Early Enzyme Replacement Therapy Does Not Prevent the Protein Losing Enteropathy Syndrome in Neurovisceral Gaucher Disease

Gaucher disease (GD) is a rare lysosomal storage disorder characterized by multisystemic involvement. With the advent of enzyme replacement therapy (ERT), patient survival has improved, revealing new long-term complications. We report a case of a 4-year-old male with severe neurovisceral GD who developed protein-losing enteropathy (PLE) secondary to mesenteric lymphadenopathy, despite ERT starting in the neonatal period. Furthermore, we review the literature related to this rare complication. The patient presented with severe recurrent diarrhea, abdominal distension, weight loss, and malnutrition. Abdominal CT revealed multiple enlarged mesenteric lymph nodes with calcification. Laboratory findings showed lymphopenia and increased fecal alpha-1-antitrypsin. Other causes of diarrhea were excluded. Treatment with a specific diet (high-protein, MCT-enriched) and a course of budesonide resulted in persistent clinical improvement and normalization of laboratory parameters. This case highlights the emergence of gastrointestinal complications in patients with neurovisceral GD on long-term ERT, particularly the development of PLE due to mesenteric lymphadenopathy. It underscores the need for vigilance in monitoring GD patients for such complications and demonstrates the potential efficacy of dietary interventions and anti-inflammatory therapy in managing PLE in this context. The case also emphasizes the limitations of current ERT in addressing all aspects of GD, particularly in sequestered sites like lymph nodes, and calls for new therapeutic strategies to address these challenges.