Recombinant Human Insulin-Like Growth Factor-1 Treatment of Severe Growth Failure in Three Siblings with STAT5B Deficiency

Authors

Gajanthan Muthuvel, Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Sareea Salem Al Remeithi, Division of Endocrinology, Department of Pediatrics, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.
Corinne Foley, Medical Scientist Training Program, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Andrew Dauber, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Vivian Hwa, Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Philippe Backeljauw, Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Document Type

Journal Article

Publication Date

8-16-2023

Journal

Hormone research in paediatrics

DOI

10.1159/000531491

Keywords

Growth failure; Growth hormone insensitivity; Recombinant human IGF-1; STAT5B

Abstract

INTRODUCTION: Patients with homozygous recessive mutations in STAT5B have severe progressive postnatal growth failure and insulin-like growth factor-I (IGF-I) deficiency associated with immunodeficiency and increased risk of autoimmune and pulmonary conditions. This report describes the efficacy and safety of recombinant human IGF-1 (rhIGF-1) in treating severe growth failure due to STAT5B deficiency. CASE PRESENTATION: Three siblings (P1, 4.4 year-old female; P2, 2.3 year-old male; and P3, 7 month-old female) with severe short stature (height SDS [HtSDS] -6.5, -4.9, -5.3, respectively) were referred to the Center for Growth Disorders at Cincinnati Children's Hospital Medical Center. All three had a homozygous mutation (p.Trp631*) in STAT5B. Baseline IGF-I was 14.7, 14.1, and 10.8 ng/mL, respectively (all < -2.5 SDS for age and sex), and IGFBP-3 was 796, 603, and 475 ng/mL, respectively (all < -3 SDS for age and sex). The siblings were started on rhIGF-1 at 40 μg/kg/dose twice daily subcutaneously (SQ), gradually increased to 110-120 μg/kg/dose SQ twice daily as tolerated. HtSDS and height velocity (HV) were monitored over time. RESULTS: Six years of growth data was utilized to quantify growth response in the two older siblings and 5 years of data in the youngest. Pre-treatment HVs were, respectively, 3.0 (P1), 3.0 (P2), and 5.2 (P3) cm/year. With rhIGF-1 therapy, HVs increased to 5.2-6.0, 4.8-7.1, and 5.5-7.4 cm/year, respectively, in the first 3 years of treatment, before they decreased to 4.7, 3.8, and 4.3 cm/year, respectively, at a COVID-19 pandemic delayed follow-up visit and with decreased treatment adherence. ΔHtSDS for P1 and P2 was +2.21 and +0.93, respectively, over 6 years, but -0.62 for P3 after 5 years and in the setting of severe local lipohypertrophy and suboptimal weight gain. P3 also experienced hypoglycemia that limited our ability to maintain target rhIGF-1 dosing. CONCLUSION: The response to rhIGF-1 therapy is less than observed with rhIGF-1 therapy for patients previously described with severe primary IGF-I deficiency, including patients with documented defects in the growth hormone receptor, but may still provide patients with STAT5B deficiency with an opportunity to prevent worsening growth failure.

APA Citation

Muthuvel, Gajanthan; Al Remeithi, Sareea Salem; Foley, Corinne; Dauber, Andrew; Hwa, Vivian; and Backeljauw, Philippe, "Recombinant Human Insulin-Like Growth Factor-1 Treatment of Severe Growth Failure in Three Siblings with STAT5B Deficiency" (2023). GW Authored Works. Paper 3243.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3243

Department

Pediatrics