We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Phenotypic spectrum and responses to recombinant human IGF1 (rhIGF1) therapy in patients with homozygous intronic pseudoexon growth hormone receptor mutation.
- Authors
Chatterjee, Sumana; Shapiro, Lucy; Rose, Stephen J.; Mushtaq, Talat; Clayton, Peter E.; Ten, Svetlana B.; Bhangoo, Amrit; Kumbattae, Uma; Dias, Renuka; Savage, Martin O.; Metherel, Louise A.; Storr, Helen L.
- Abstract
Background: Patients with homozygous intronic pseudoexon GH receptor (GHR) mutations (6) have growth hormone insensitivity (GHI) (growth failure, IGF1 deficiency and normal/elevated serum GH). We report 9 patients in addition to previously described 11 GHR 6 patients and their responses to rhIGF1 therapy. Methods: 20 patients (12 males, 11 families, mean age 4.0 ± 2.2 years) were diagnosed genetically in our centre. Phenotypic data and responses to rhIGF1 treatment were provided by referring clinicians. Continuous parametric variables were compared using Student t-test or ANOVA. Results: 10/20 (50%) had typical facial features of GHI, 19/20 (95%) from consanguineous families and 18/20 (90%) of Pakistani origin. At diagnosis, mean height SDS: -4.1 ± 0.95, IGF1 SDS: -2.8 ± 1.4; IGFBP3 SDS: -3.0 ± 2.1 and mean basal and peak GH levels: 11.9 µg/L and 32.9 µg/L, respectively. 1/12 who had IGF1 generation test, responded (IGF1: 132-255 ng/mL). 15/20 (75%; 11M) received rhIGF1 (mean dose: 114 µg/kg twice daily, mean duration: 5.3 ± 2.5 years). Mean baseline height velocity of 4.7 ± 1.1 cm/year increased to 7.4 ± 1.8 cm/year (P = 0.001) during year 1 of therapy. Year 3 mean height SDS (-3.2 ± 1.0) was higher than pre-treatment height SDS (-4.3 ± 0.8) (P = 0.03). Mean cumulative increase in height SDS after year 5 was 1.4 ± 0.9. Difference between target height (TH) SDS and adult or latest height SDS was less than that of TH SDS and pre-treatment height SDS (2.1 ± 1.2 vs 3.0 ± 0.8; P = 0.02). Conclusion: In addition to phenotypic heterogeneity in the cohort, there was mismatch between clinical and biochemical features in individual patients with 6 GHR mutations. rhIGF1 treatment improved height outcomes.
- Subjects
GENETIC disorder treatment; HUMAN phenotype; EXONS (Genetics); SOMATOTROPIN receptors; SOMATOMEDIN C; RECOMBINANT proteins; GENETIC disorder diagnosis
- Publication
European Journal of Endocrinology, 2018, Vol 178, Issue 5, p481
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-18-0042