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PHENOTYPIC SPECTRUM AND RESPONSES TO RECOMBINANT HUMAN IGF1 (rhIGF1) THERAPY IN PATIENTS WITH HOMOZYGOUS INTRONIC PSEUDOEXON GROWTH HORMONE RECEPTOR MUTATION.

Chatterjee, Sumana and Shapiro, Lucy and Rose, Stephen J and Mushtaq, Talat and Clayton, Peter E and Ten, Svetlana and Bhangoo, Amrit and Kumbattae, Uma and Dias, Renuka and Savage, Martin O and Metherell, Louise A and Storr, Helen L (2018) PHENOTYPIC SPECTRUM AND RESPONSES TO RECOMBINANT HUMAN IGF1 (rhIGF1) THERAPY IN PATIENTS WITH HOMOZYGOUS INTRONIC PSEUDOEXON GROWTH HORMONE RECEPTOR MUTATION. European journal of endocrinology. ISSN 1479-683X.

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Official URL: http://www.eje-online.org/content/early/2018/03/02...

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.

Item Type: Article
Subjects: WH Haemic and lymphatic systems. Haematology
Divisions: Womens and Childrens > Paediatrics
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Depositing User: Miss Emily Johnson
Date Deposited: 09 Mar 2018 15:52
Last Modified: 09 Mar 2018 15:52
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1620

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