Delayed growth and puberty in patients with Gaucher disease type 1: Natural history and effect of splenectomy and/or enzyme replacement therapy

Background: Growth retardation in childhood was only recently recognized as a prominent feature of Gaucher disease type 1, but there are few data on b oth the pubertal development and the final outcome of growth and sexual mat uration. Objective: To investigate the natural pattern of growth and puberty in pati ents with Gaudier disease type 1 and the effect of splenectomy and enzyme r eplacement therapy. Methods: We retrospectively analyzed growth and puberty in 57 patients with Gaucher disease type 1; 52 were followed since childhood and/or prepuberty and 42 have reached sexual maturity and final height. In the analysis we c onsidered severity of disease, time of splenectomy, and start of enzyme rep lacement therapy. Results: Deceleration of growth at age 3-5 years was observed in 30 of 57 p atients followed since early childhood while untreated: height-SDS decrease d from -034+/-0.42 at age 0-3 years to -1.93+/-0.95 (P<0.01) at age 7-10 ye ars and was more pronounced with severe disease. A high prevalence (59.6%) of delayed puberty, which was more frequent with severe disease, was observ ed in 47 patients followed before and throughout puberty. No primary endocr ine pathology was found. All patients, untreated as well as treated, with g rowth and pubertal delay had a spontaneous catch-up, achieved full sexual m aturation, and most (83.3%) reached a final height within the range of pare ntal height-standard deviation score. Splenectomy (partial and/or total) pe rformed in 20 patients while still growing had a beneficial effect on growt h, which was temporary in some and did not affect puberty. ERT improved gro wth in 11 patients who started therapy before puberty, as evidenced by a pr ogressive increase in the height-SDS, and seemed to normalize the onset of puberty. Conclusions: Growth retardation in childhood and delay of puberty are chara cteristic of Gaucher disease type 1 and are more frequent with severe disea se. There is a spontaneous catch-up later in life and most patients reach a final height within their genetic growth potential. Enzyme replacement the rapy apparently normalizes growth and possibly also the onset of puberty.