背景:严重身材矮小是肢端畸形的特征,但是关于增长的数据很少。一些中心使用重组人生长激素(rhGH)治疗来增加最终身高,但是到目前为止还没有发表任何研究。我们的目标是进行多中心,回顾性,队列研究,以调查两种类型的肢端勃起的个体的生长,是否用rhGH治疗;我们使用新的命名法来描述肢端肌痉挛,由于该疾病属于PTH/PTHrP信号传导障碍(iPPSD)的一大组;肢端肌痉挛是指iPPSD4(由于PRKAR1A突变导致的肢端肌痉挛1型)和iPPSD5(由于PDE4D突变导致的肢端肌痉挛2型).
方法:我们提供了具有iPPSD4基因特征的个体和具有iPPSD5临床特征的参与者的营养数据。
结果:我们分别纳入了20名和17名iPPSD4和iPPSD5患者。rhGH治疗的iPPSD4患者(n=9)出生时小于未接受rhGH的患者(中位数-2.2SDSvs.-1.7SDS);他们在rhGH治疗期间显示出追赶增长的趋势(第一年中位数为0.5SDS)。与未接受rhGH的患者(n=4)相比,接受rhGH治疗的患者(n=5)达到了更好的最终身高(中位数-2.8SDSvs.-3.9SDS),这表明rhGH能有效增加这些患者的身高。对于未使用rhGH处理的iPPSD4,目标高度与最终高度的差异在1.6和3.0SDS之间(n=4),2.1-2.8rhGH处理的iPPSD4的SDS(n=5),未经rhGH处理的iPPSD5为0.6-5.5SDS(n=5),rhGH处理的iPPSD5为2.5-3.1(n=2)。
结论:rhGH可能对肢端性勃起/iPPSD患者的最终身高有积极影响。我们接受rhGH治疗的队列开始治疗相对较晚,这也许可以解释,至少在某种程度上,rhGH对身高的影响有限。
BACKGROUND: Severe short stature is a feature of
acrodysostosis, but data on growth are sparse. Treatment with recombinant human growth hormone (rhGH) is used in some centers to increase final height, but no studies have been published so far. Our objective was to conduct a multicenter, retrospective, cohort study to investigate growth in individuals with both types of acrodysostosis, treated with rhGH or not; we used the new nomenclature to describe
acrodysostosis, as this disease belongs to the large group of inactivating PTH/PTHrP signaling disorders (iPPSD);
acrodysostosis refers to iPPSD4 (
acrodysostosis type 1 due to PRKAR1A mutations) and iPPSD5 (
acrodysostosis type 2, due to PDE4D mutations).
METHODS: We present auxological data from individuals with genetically characterized iPPSD4, and participants with clinical features of iPPSD5.
RESULTS: We included 20 and 17 individuals with iPPSD4 and iPPSD5, respectively. The rhGH-treated iPPSD4 patients (n = 9) were smaller at birth than those who did not receive rhGH (median - 2.2 SDS vs. - 1.7 SDS); they showed a trend to catch-up growth during rhGH therapy (median 0.5 SDS in the first year). The rhGH-treated patients (n = 5) reached a better final height compared to those who did not receive rhGH (n = 4) (median - 2.8 SDS vs. - 3.9 SDS), suggesting that rhGH is efficient to increase height in those patients. The difference in target height to final height ranged between 1.6 and 3.0 SDS for iPPSD4 not treated with rhGH (n = 4), 2.1-2.8 SDS for rhGH-treated iPPSD4 (n = 5), 0.6-5.5 SDS for iPPSD5 not treated with rhGH (n = 5) and 2.5-3.1 for rhGH-treated iPPSD5 (n = 2).
CONCLUSIONS: Final height may be positively influenced by rhGH in patients with
acrodysostosis/iPPSD. Our rhGH-treated cohort started therapy relatively late, which might explain, at least in part, the limited effect of rhGH on height.