Treatment of Short Stature in Aggrecan-deficient Patients With Recombinant Human GH: 3-year Response.

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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 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). 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.