Gajanthan Muthuvel1, Andrew Dauber2,3, Eirene Alexandrou4,5, Leah Tyzinski1, Melissa Andrew2, Vivian Hwa1,6, Philippe Backeljauw1,6. 1. Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. 2. Division of Endocrinology, Children's National Hospital, Washington, DC 20010, USA. 3. Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA. 4. Division of Endocrinology, The University of Iowa Stead Family Children's Hospital, Iowa City, IA 52242, USA. 5. Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA. 6. Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA.
Abstract
CONTEXT: Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, often with advanced skeletal maturation and premature growth cessation. There is a paucity of information on the effects of growth-promoting interventions. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of recombinant human growth hormone (rhGH) therapy on linear growth in children with ACAN deficiency. METHODS: Open-label, single-arm, prospective study at Cincinnati Children's Hospital Medical Center. Ten treatment-naïve patients were recruited. Inclusion criteria were a confirmed heterozygous mutation in ACAN, age ≥2 years, prepubertal, bone age (BA) ≥chronological age (CA), and normal insulin-like growth factor I concentration. Treatment was with rhGH (50 µg/kg/day) over 1 year. Main outcomes measured were height velocity (HV) and change in (Δ) height SD score (HtSDS). RESULTS: Ten patients (6 females) were enrolled with median CA of 5.6 years (range 2.4-9.7). Baseline median HtSDS was -2.5 (range -4.3 to -1.1). Median baseline BA was 6.9 years (range 2.5-10.0), with median BA/CA of 1.2 (range 0.9-1.5). Median pretreatment HV was 5.2 cm/year (range 3.8-7.1), increased to 8.3 cm/year (range 7.3-11.2) after 1 year of therapy (P = .004). Median ΔHtSDS after 1 year was +0.62 (range +0.35 to +1.39) (P = .002). Skeletal maturation did not advance inappropriately (median ΔBA/CA -0.1, P = .09). No adverse events related to rhGH were observed. CONCLUSION: Treatment with rhGH improved linear growth in a cohort of patients with short stature due to ACAN deficiency.
CONTEXT: Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, often with advanced skeletal maturation and premature growth cessation. There is a paucity of information on the effects of growth-promoting interventions. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of recombinant human growth hormone (rhGH) therapy on linear growth in children with ACAN deficiency. METHODS: Open-label, single-arm, prospective study at Cincinnati Children's Hospital Medical Center. Ten treatment-naïve patients were recruited. Inclusion criteria were a confirmed heterozygous mutation in ACAN, age ≥2 years, prepubertal, bone age (BA) ≥chronological age (CA), and normal insulin-like growth factor I concentration. Treatment was with rhGH (50 µg/kg/day) over 1 year. Main outcomes measured were height velocity (HV) and change in (Δ) height SD score (HtSDS). RESULTS: Ten patients (6 females) were enrolled with median CA of 5.6 years (range 2.4-9.7). Baseline median HtSDS was -2.5 (range -4.3 to -1.1). Median baseline BA was 6.9 years (range 2.5-10.0), with median BA/CA of 1.2 (range 0.9-1.5). Median pretreatment HV was 5.2 cm/year (range 3.8-7.1), increased to 8.3 cm/year (range 7.3-11.2) after 1 year of therapy (P = .004). Median ΔHtSDS after 1 year was +0.62 (range +0.35 to +1.39) (P = .002). Skeletal maturation did not advance inappropriately (median ΔBA/CA -0.1, P = .09). No adverse events related to rhGH were observed. CONCLUSION: Treatment with rhGH improved linear growth in a cohort of patients with short stature due to ACAN deficiency.
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