Growth hormone — past, present and future

Developmen

The continuum between GH deficiency and GH insensitivity in children

The continuum of growth hormone (GH)-IGF-I axis defects extends from severe to mild GH deficiency, through short stature disorders of undefined aetiology, to GH insensitivity disorders which can also be mild or severe. This group of defects comprises a spectrum of endocrine, biochemical, phenotypic and genetic abnormalities. The extreme cases are generally easily diagnosed because they conform to well-studied phenotypes with recognised biochemical features. The milder cases of both GH deficiency and GH insensitivity are less well defined and also overlap with the group of short stature conditions, labelled as idiopathic short stature (ISS). In this review the continuum model, which plots GH sensitivity against GH secretion, will be discussed. Defects causing GH deficiency and GH insensitivity will be described, together with the use of a diagnostic algorithm, designed to aid investigation and categorisation of these defects. The continuum will also be discussed in the context of growth-promoting endocrine therapy

Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome)

Background: The skeletal phenotype of mucopolysaccharidosis VI (MPS VI) is characterized by short stature and growth failure. Objective: The purpose of this study was to construct reference growth curves for MPS VI patients with rapidly and slowly progressive disease. Methods: We pooled cross-sectional and longitudinal height for age data from galsulfase (Naglazyme(®), BioMarin Pharmaceutical Inc.), treatment naïve patients (n = 269) who participated in various MPS VI studies, including galsulfase clinical trials and their extension programs, the MPS VI clinical surveillance program (CSP), and the MPS VI survey and resurvey studies, to construct growth charts for the MPS VI population. There were 229 patients included in this study, of which data from 207 patients ≤25 years of age with 513 height measurements were used for constructing reference growth curves. Results: Height for age growth curves for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were constructed for patients with rapidly and slowly progressing disease defined by the pre-enzyme replacement therapy (ERT) uGAG levels of > or ≤200 μg/mg creatinine. The mean (SD) pre-ERT uGAG levels were 481.0 (218.6) and 97.8 (56.3) μg/mg creatinine for the patients ≤25 years of age with rapidly (n = 131) and slowly (n = 76) progressing MPS VI disease, respectively. The median growth curves for patients with ≤ and >200 μg/mg creatinine were above and below the median (50th percentile) growth curve for the entire MPS VI population. Conclusion: MPS VI growth charts have been developed to assist in the clinical management of MPS VI patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this chapter (doi:10.1007/8904_2014_333) contains supplementary material, which is available to authorized users