Muthuvel Gajanthan, Dauber Andrew, Alexandrou Eirene, Tyzinski Leah, Hwa Vivian, Backeljauw Philippe
Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45267, USA.
J Endocr Soc. 2024 Oct 10;8(12):bvae177. doi: 10.1210/jendso/bvae177. eCollection 2024 Oct 29.
Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, as well as early-onset joint disease.
The objective of this study was to evaluate the efficacy and safety of recombinant human GH (rhGH) on linear growth in ACAN-deficient children.
Open-label, single-arm, prospective study over 3 years recruiting 10 treatment-naïve patients with heterozygous mutations in , age ≥2 years, prepubertal, and normal IGF-I concentration. Patients were treated with rhGH (initially, 50 mcg/kg/day). Main outcomes were change in (Δ) height SD score (HtSDS) and height velocity (HV).
Ten patients (6 females) enrolled with median chronological age (CA) of 5.6 years (range, 2.4-9.7). Baseline median HtSDS, HV, and bone age/CA were -2.5 (range, -4.3 to -1.1), 5.2 cm/year (range, 3.8 to 7.1), and 1.2 (range, 0.9 to 1.5), respectively. The cumulative median ΔHtSDS over 3 years was +1.21 (range, +0.82 to +1.94). Median HV increased to 8.3 cm/year (range, 7.3-11.2), 7.7 cm/year (range, 5.9-8.8), and 6.8 cm/year (range, 4.9-8.6) during years 1, 2, and 3, respectively. The median Δ predicated adult height was +6.8 cm over 3 years. Four female subjects entered puberty; nevertheless, median Δbone age/CA was -0.1. No adverse events related to rhGH were observed.
Linear growth improved in a cohort of ACAN-deficient patients treated with rhGH, albeit somewhat attenuated in older participants who entered puberty. Longitudinal follow-up is needed to assess the long-term efficacy of rhGH and adult height outcome.
聚集蛋白聚糖（ACAN）缺乏症患者表现为常染色体显性遗传的身材矮小以及早发性关节疾病。
本研究旨在评估重组人生长激素（rhGH）对ACAN缺乏症儿童线性生长的疗效和安全性。
一项为期3年的开放标签、单臂、前瞻性研究，招募了10名年龄≥2岁、青春期前、胰岛素样生长因子-I（IGF-I）浓度正常且未接受过治疗的杂合突变患者。患者接受rhGH治疗（初始剂量为50μg/kg/天）。主要结局指标为身高标准差评分（HtSDS）的变化（Δ）和身高增长速度（HV）。
10名患者（6名女性）入组，中位实足年龄（CA）为5.6岁（范围为2.4 - 9.7岁）。基线时，中位HtSDS、HV和骨龄/实足年龄分别为-2.5（范围为-4.3至-1.1）、5.2cm/年（范围为3.8至7.1）和1.2（范围为0.9至1.5）。3年期间累积的中位ΔHtSDS为+1.21（范围为+0.82至+1.94）。第1年、第2年和第3年的中位HV分别增加到8.3cm/年（范围为7.3 - 11.2）、7.7cm/年（范围为5.9 - 8.8）和6.8cm/年（范围为4.9 - 8.6）。3年期间预测成年身高的中位Δ为+6.8cm。4名女性受试者进入青春期；然而，中位Δ骨龄/实足年龄为-0.1。未观察到与rhGH相关的不良事件。
接受rhGH治疗的ACAN缺乏症患者队列的线性生长有所改善，不过在进入青春期的年长参与者中改善程度有所减弱。需要进行纵向随访以评估rhGH的长期疗效和成年身高结局。
