Related Experiment Video
Updated: Jul 19, 2025
Author Spotlight: Advancements and Challenges in β-Cells Differentiation from Pluripotent Stem Cells
Published on: February 2, 2024
Recombinant Human Insulin-Like Growth Factor-1 Treatment of Severe Growth Failure in Three Siblings with STAT5B
Gajanthan Muthuvel1, Sareea Salem Al Remeithi2, Corinne Foley3
1Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Insights
Recombinant human insulin-like growth factor-1 (rhIGF-1) therapy in STAT5B deficiency showed improved growth velocity but less overall height gain compared to other conditions. This treatment may help prevent worsening growth failure in these patients.
Area of Science:
- Genetics and Endocrinology
- Investigating the molecular basis of growth disorders
- Evaluating therapeutic interventions for rare genetic conditions
Background:
- STAT5B deficiency causes severe postnatal growth failure and insulin-like growth factor-I (IGF-I) deficiency.
- Associated conditions include immunodeficiency, autoimmune disorders, and pulmonary issues.
- This study assesses recombinant human IGF-1 (rhIGF-1) efficacy in STAT5B-deficient patients.
Observation:
- Three siblings with STAT5B mutations and severe short stature were treated with rhIGF-1.
- Initial treatment increased height velocity significantly in all siblings.
- Long-term data showed diminished growth response and challenges with adherence and side effects like hypoglycemia and lipohypertrophy.
Findings:
- rhIGF-1 therapy increased height velocity in STAT5B-deficient siblings.
- Overall height standard deviation score (SDS) gains were modest (+2.21 and +0.93 for two siblings) and negative for one (-0.62).
- Growth response was less pronounced than in patients with primary IGF-I deficiency or growth hormone receptor defects.
Implications:
- rhIGF-1 may offer a therapeutic option to mitigate growth failure in STAT5B deficiency.
- Treatment outcomes appear less robust compared to other severe IGF-I deficiencies.
- Further research is needed to optimize rhIGF-1 dosing and management strategies for STAT5B deficiency.
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.
Related Concept Videos
01:16Insulin: Dosing Regimen and Adverse Effects
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
01:28Role of Hematopoietic Growth Factors
Thrombopoietin (TPO), mainly released by the liver,...
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:16TGF - β Signaling Pathway
01:25Insulin: Biosynthesis, Chemistry, and Preparation
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...