Abstract
Background: Patients with homozygous intronic pseudoexon GH receptor(GHR) mutations(6Ψ) 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 6Ψ patients and their responses to rhIGF1 therapy.
Methods: 20 patients (12 males, 11 families, mean age 4.0±2.2yrs) 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 to 255 ng/ml). 15/20 (75%; 11M) received rhIGF1(mean dose 114 micrograms/kg twice daily, mean duration: 5.3 ± 2.5yrs). Mean baseline height velocity of 4.7 ± 1.1cm/yr increased to 7.4 ± 1.8cm/yr(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 pretreatment 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 6Ψ GHR mutations. rhIGF1 treatment improved height outcomes
Methods: 20 patients (12 males, 11 families, mean age 4.0±2.2yrs) 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 to 255 ng/ml). 15/20 (75%; 11M) received rhIGF1(mean dose 114 micrograms/kg twice daily, mean duration: 5.3 ± 2.5yrs). Mean baseline height velocity of 4.7 ± 1.1cm/yr increased to 7.4 ± 1.8cm/yr(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 pretreatment 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 6Ψ GHR mutations. rhIGF1 treatment improved height outcomes
| Original language | English |
|---|---|
| Journal | European Journal of Endocrinology |
| Early online date | 2 Mar 2018 |
| DOIs | |
| Publication status | Published - 2018 |