Agnès Linglart

Background Maternal inactivating GNAS mutations lead to pseudohypoparathyroidism 1A (PHP1A), newly classified as inactivating parathyroid hormone (PTH)/PTHrP-signaling disorder type 2 of maternal inheritance (iPPSD2). Patients present with resistance to PTH and other hormones, subcutaneous ossifications, brachydactyly, short stature, and early-onset obesity. They can be born small for gestational age (SGA) and may present with growth hormone (GH) deficiency. The use of recombinant human GH (rhGH) therapy has been sporadically reported, yet we lack data on the long-term efficacy and safety of rhGH, as well as on adult height. Objective Our multicenter, retrospective, observational study describes growth in patients treated with rhGH in comparison with untreated iPPSD2/PHP1A controls. Methods We included 190 patients, of whom 26 received rhGH. Height, weight, body mass index at various time points, and adult height were documented. We analyzed the effect of rhGH on adult height by using linear mixed models. Results Adult height was available for 11/26 rhGH-treated individuals and for 69/164 controls. Patients treated with rhGH showed a gain in height of 0.7 standard deviation scores (SDS) after 1 year (CI +0.5 to +0.8, P < .001) and of 1.5 SDS after 3 years (CI +1.0 to +2.0, P < .001). Additionally, there was a clear beneficial impact of rhGH on adult height when compared with untreated controls, with a difference of 1.9 SDS (CI +1.1 to +2.7, P < .001). Body mass index SDS did not vary significantly upon rhGH therapy. Conclusion Recombinant human growth hormone treatment of iPPSD2/PHP1A patients with short stature improves growth and adult height. More studies are needed to confirm long-term efficacy and safety.

Context Musculoskeletal complications are the main manifestations in adults with X-linked hypophosphatemia (XLH). Enthesopathy significantly impairs quality of life. Objective To identify the risk factors associated with the development and progression of spinal enthesopathies in adults with XLH. Design and setting We conducted a retrospective study in the French Reference Center for Rare Diseases of the Calcium and Phosphate Metabolism. Patients Adults XLH patients with 2 EOS® imaging performed at least 2 years apart at the same center between June 2011 and March 2022. The progression of enthesopathies was defined as a new enthesopathy at least 1 intervertebral level in patients with or without presence of enthesopathy at baseline. Main outcome measures Demographic, treatment, PHEX mutation with the progression of enthesopathies. Results Fifty-one patients (66.7% of women, mean age 42.1 ± 13.4 years) underwent 2 EOS imaging with an average interval of 5.7 (± 2.31) years. Progression of spinal enthesopathies was observed in 27 (52.9%) patients. In univariate analysis, patients with a progression of spinal enthesopathies were significantly older (P < .0005), were significantly older at treatment initiation (P = .02), presented with dental complications (P = .03), received less frequently treatment during childhood with phosphate and/or vitamin D analogs (P = .06), and presented more frequently with hip osteoarthritis (P = .002) at baseline. In multivariate analysis, none of these factors was associated with a progression of spinal enthesopathies. Conclusion This study confirms the high proportion of patients with a progression of spinal enthesopathies. Age seems to be the main factor associated with progression.