Treatment of Short Stature in Aggrecan Deficient Patients with Recombinant Human Growth Hormone: Three-Year Response

Gajanthan Muthuvel; Andrew Dauber; Eirene Alexandrou; Leah Tyzinski; Vivian Hwa; Philippe Backeljauw

doi:10.1210/jendso/bvae177

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Treatment of Short Stature in Aggrecan Deficient Patients with Recombinant Human Growth Hormone: Three-Year Response

Journal article

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Peer reviewed

Treatment of Short Stature in Aggrecan Deficient Patients with Recombinant Human Growth Hormone: Three-Year Response

Gajanthan Muthuvel, Andrew Dauber, Eirene Alexandrou, Leah Tyzinski, Vivian Hwa and Philippe Backeljauw

Journal of the Endocrine Society, Vol.8(12), bvae177

10/29/2024

DOI: 10.1210/jendso/bvae177

PMCID: PMC11535719

PMID: 39502477

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Abstract

Abstract 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 growth hormone (rhGH) on linear growth in ACAN deficient children. Methods Open-label, single-arm, prospective study over three years recruiting ten treatment-naïve patients with heterozygous mutations in ACAN, age ≥2 years, pre-pubertal, and normal IGF-I concentration. Patients were treated with rhGH (initially 50 mcg/kg/day). Main outcomes were change in (Δ) height standard deviation score (HtSDS) and height velocity (HV). Results Ten patients (six females) enrolled with median chronological (CA) of 5.6 yrs (range 2.4 to 9.7). Baseline median HtSDS, HV, and bone age (BA)/CA were -2.5 (range -4.3 to -1.1), 5.2 cm/yr (range 3.8 to 7.1), and 1.2 (range, 0.9 to 1.5), respectively. The cumulative median ΔHtSDS over three years was +1.21 (range +0.82 to +1.94). Median HV increased to 8.3 cm/yr (range 7.3 to 11.2), 7.7 cm/yr (range 5.9 to 8.8), and 6.8 cm/yr (range 4.9 to 8.6) during years one, two, and three, respectively. The median Δ predicated adult height was +6.8 cm over three years. Four female subjects entered puberty, nevertheless, median ΔBA/CA was -0.1. No adverse events related to rhGH were observed. Conclusions 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.

Aggrecan deficiency

short stature

growth hormone

Details

Title: Subtitle: Treatment of Short Stature in Aggrecan Deficient Patients with Recombinant Human Growth Hormone: Three-Year Response
Creators: Gajanthan Muthuvel - Cincinnati Children's Hospital Medical Center
Andrew Dauber - Children's National
Eirene Alexandrou - University of Iowa
Leah Tyzinski - Cincinnati Children's Hospital Medical Center
Vivian Hwa - Cincinnati Children's Hospital Medical Center
Philippe Backeljauw - Cincinnati Children's Hospital Medical Center
Resource Type: Journal article
Publication Details: Journal of the Endocrine Society, Vol.8(12), bvae177
DOI: 10.1210/jendso/bvae177
PMID: 39502477
PMCID: PMC11535719
NLM abbreviation: J Endocr Soc
ISSN: 2472-1972
eISSN: 2472-1972
Publisher: ENDOCRINE SOC
Grant note: Novo Nordisk Inc.
This study was generously supported by a grant from Novo Nordisk Inc. Statistical support was graciously provided by Katherine Bowers, PhD.
Language: English
Electronic publication date: 10/10/2024
Date published: 10/29/2024
Academic Unit: Endocrinology and Diabetes; Stead Family Department of Pediatrics
Record Identifier: 9984736599202771

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