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Treatment of Short Stature in Aggrecan-deficient Patients With Recombinant Human GH: 3-year Response
Gajanthan Muthuvel1,2, Andrew Dauber3,4, Eirene Alexandrou5,6
1Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Insights
Recombinant human growth hormone (rhGH) treatment improved linear growth in children with aggrecan (ACAN) deficiency, leading to increased height. Long-term outcomes require further study, especially for older participants entering puberty.
Area of Science:
- Pediatric Endocrinology
- Genetics
- Growth Disorders
Background:
- Aggrecan (ACAN) deficiency causes short stature and early-onset joint disease.
- Understanding growth patterns in ACAN deficiency is crucial for effective treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of recombinant human growth hormone (rhGH) in improving linear growth in children with ACAN deficiency.
- To assess changes in height standard deviation score (HtSDS) and height velocity (HV) over a 3-year period.
Main Methods:
- An open-label, single-arm, prospective study.
- Recruited 10 treatment-naïve children with ACAN deficiency (heterozygous mutations), aged 2 years or older, prepubertal, with normal IGF-I.
- rhGH treatment (50 mcg/kg/day) was administered for 3 years, monitoring HtSDS and HV.
Main Results:
- Median HtSDS increased by +1.21 over 3 years, with a significant boost in median HV.
- Median HV increased from a baseline of 5.2 cm/year to 8.3 cm/year in year 1.
- Predicted adult height increased by a median of 6.8 cm; no adverse events were reported.
Conclusions:
- rhGH treatment demonstrates efficacy in improving linear growth in ACAN-deficient children.
- Growth response may be attenuated in older children entering puberty.
- Longitudinal follow-up is necessary to determine long-term efficacy and final adult height.
Context:
Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, as well as early-onset joint disease.
Objective:
The objective of this study was to evaluate the efficacy and safety of recombinant human GH (rhGH) on linear growth in ACAN-deficient children.
Methods:
Open-label, single-arm, prospective study over 3 years recruiting 10 treatment-naïve patients with heterozygous mutations in ACAN, 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).
Results:
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.
Conclusion:
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.
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