Endocrine Abstracts

Since the first description of pseudohypoparathyroidism (PHP) a remarkable clinical variability 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. PHP and related disorders vary in clinical presentation and disease severity, and clinical features usually develop during mid and late childhood. There are only few reports in literature about neonatal PHP, describing hypocalcemic seizures in late neonatal period. To our knowledge no others neonatal complications are described as associated to iPPSD. The aim of this study is to analyse a large cohort of iPPSD patients and to investigate early history of the disease, 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 Fondazione IRCCS Ca’ Granda 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 then investigated the rate of neonatal complications occurring within the first month of life. Then, we have subdivided neonatal complications in several categories (respiratory, cardiac, neurological, gastrointestinal, metabolic, multiple districts, others) and we have assessed the number of complications for each patient. We analysed data from 83 children and 53 adults with diagnosis of iPPSD (mean age 18 ± 11 years). In our cohort 55.9% of patients were diagnosed with iPPSD2 (PHP1A) and 17.6% with iPPSD3 (PHP1B), 11.8% of patients suffered from acrodysostosis type 1 or 2 and 2.2% had a mutation of PTHR1 (iPPSD1). In 12.5% of cases we couldn’t find any mutations (iPPSDx). At least one neonatal complication occurred in 36% of patients (49/136). iPPSD2 patients represent the majority of our cohort and 47% of them experienced neonatal complications, being the category the most affected (P=0.001). At univariate analysis neonatal complications in iPPSD patients correlate with the risk of developing neurocognitive impairment (P=0.01) and constipation (P=0.04) later in life. Moreover, 38.9% iPPSD2 patients who developed neonatal complications had > 2 complications at birth. We could also identify recurrent complications among iPPSD2 patients: 8 of them (10.5%) developed neonatal hypoglicemia and 13 (18.4%) experienced transient respiratory distress. To now we can conclude that iPPSD and especially iPPSD2 newborns need special care at birth, for the risk of developing neonatal complications.