AP-HP, Department of Endocrinology and Diabetology for Children and Department of Adolescent Medicine, Bicêtre Paris-Saclay University Hospital, 78 Rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France.
AP-HP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Saclay, Bicêtre Paris-Saclay Hospital, 78 Rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France.
J Endocrinol Invest. 2023 Aug;46(8):1673-1684. doi: 10.1007/s40618-023-02026-2. Epub 2023 Feb 7.
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).
We present auxological data from individuals with genetically characterized iPPSD4, and participants with clinical features of iPPSD5.
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).
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.
肢端发育不良症的一个特征是严重身材矮小，但关于生长的数据很少。在一些中心，使用重组人生长激素（rhGH）治疗来增加最终身高，但迄今为止尚无研究发表。我们的目的是进行一项多中心、回顾性队列研究，以调查接受或未接受 rhGH 治疗的两种类型肢端发育不良症患者的生长情况；我们使用新的命名法来描述肢端发育不良症，因为这种疾病属于失活甲状旁腺素/甲状旁腺素相关肽信号障碍（iPPSD）的大组；肢端发育不良症是指 iPPSD4（由于 PRKAR1A 突变引起的 1 型肢端发育不良症）和 iPPSD5（由于 PDE4D 突变引起的 2 型肢端发育不良症）。
我们介绍了具有基因特征的 iPPSD4 个体和具有 iPPSD5 临床特征的个体的人体测量数据。
我们纳入了 20 名 iPPSD4 患者和 17 名 iPPSD5 患者。rhGH 治疗的 iPPSD4 患者（n=9）出生时比未接受 rhGH 治疗的患者小（中位数-2.2 SDS 与-1.7 SDS）；他们在 rhGH 治疗期间表现出追赶生长的趋势（第一年中位数为 0.5 SDS）。接受 rhGH 治疗的患者（n=5）与未接受 rhGH 治疗的患者（n=4）相比，达到了更好的最终身高（中位数-2.8 SDS 与-3.9 SDS），这表明 rhGH 对这些患者增加身高有效。未接受 rhGH 治疗的 iPPSD4 患者（n=4）的靶身高与最终身高之间的差异在 1.6 至 3.0 SDS 之间，rhGH 治疗的 iPPSD4 患者（n=5）在 2.1-2.8 SDS 之间，未接受 rhGH 治疗的 iPPSD5 患者（n=5）在 0.6-5.5 SDS 之间，rhGH 治疗的 iPPSD5 患者（n=2）在 2.5-3.1 SDS 之间。
rhGH 可能对肢端发育不良症/iPPSD 患者的最终身高产生积极影响。我们的 rhGH 治疗队列开始治疗的时间相对较晚，这至少可以部分解释 rhGH 对身高的影响有限。
