ESPE Abstracts

Since the first description of pseudohypoparathyroidism (PHP), a remarkable clinical variability, which translates in several PHP subtypes, was observed. In 2016 a new classification of this group of diseases have been published by the European Network on PHP and related disorders, proposing “inactivating PTH/PTHrP signaling disorder” (iPPSD) as a new term that encompasses all the clinical entities, stressing the common mechanism responsible for all diseases. iPPSDs vary in clinical presentation and disease severity, and the clinical features usually develop during mid and late childhood. There are only few reports in literature about neonatal and early infancy iPPSDs, describing patients who presented with hypocalcemic seizures in late neonatal or early infantile period. To our knowledge no others neonatal complications are described as associated to iPPSDs. The aim of this study is to describe a large cohort of iPPSDs patients, with special focus on neonatal complications. We collected data from 136 patients diagnosed with iPPSDs and in regular follow-up at the Endocrinology Unit of Ospedale Maggiore Policlinico (Milan, Italy) and at the Pediatric Endocrinology Unit of Hôpital Bicêtre (Paris, France). We have retrospectively collected data about birth and we have investigated the rate and the severity of neonatal complications occurring in each iPPSD category. We conducted univariate and multivariate analysis to assess potential predictors of neonatal complications and correlation between neonatal complications and severity of the disease. We analysed data from 83 children and 53 adults with diagnosis of iPPSDs (81 female, mean age 18 ± 11, range 0.9 - 60.7 years). At least one neonatal complication occurred in 36% of patients. iPPSD2 patients represent the majority of our cohort (55.9%) and 47% of them experienced neonatal complications at birth, being the category more affected (P = 0.001). Neonatal complications in iPPSDs patients correlate with the risk of developing neurocognitive impairment (P = 0.02), constipation (P = 0.04) and ectopic ossification (P = 0.008) later in life. Importantly, we found no genotype/phenotype relationships in iPPSD2 patients. To now, we can conclude that iPPSDs, and especially iPPSD2, newborns need special care at birth, for the risk of developing neonatal complications. Moreover, it is worth signalling that among our total cohort of patients 79.4% developed neonatal complications or any signs of iPPSD within the first year of life. Mean age at diagnosis of our patients was 8.7 ± 7.3 (range 0.1-34) years, it becomes clear that exists a huge delay in diagnosis and maybe diagnostic criteria should be adapted for early infancy iPPSDs patients.