Background. Mesenteric lymphadenopathy is a rare manifestation of Gaucher disease (GD) in children and can be accompanied by protein losing enteropathy (PLE). PLE is a difficult-to-treat complication of GD. To date, only a few pediatric GD cases with PLE and massive mesenteric lymphadenopathies have been reported. Case. Here, we report a girl with chronic neuronopathic GD, whose disease course was complicated by massive mesenteric lymphadenopathies with resultant protein losing enteropathy despite a regular and appropriate enzyme replacement therapy of 60 IU/kg/biweekly until the development of mesenteric lymphadenopathies and 120 IU/kg/biweekly thereafter. Conclusions. PLE is a devastating and life threatening complication of GD developing despite long term use of high dose ERT. Clinicians should be alert for this complication particularly in GD patients presenting with progressive abdominal distension, edema, ascites and diarrhea or in patients who have already developed mesenteric lymphadenopathies. Timely diagnosis may allow early intervention with previously suggested surgical or medical treatment options. Although there is no specific and effective treatment, surgical and aggressive medical interventions in addition to ERT were reported to relieve diarrhea and halt progression of mesenteric lymphadenopathies.