Journal Article

Neonatal and Early Infancy Features of Patients With Inactivating PTH/PTHrP Signaling Disorders/Pseudohypoparathyroidism

Pagnano, Angela, Arosio, Maura, Linglart, Agnès, Berkenou, Jugurtha, Rothenbuhler, Anya, Del Sindaco, Giulia, Mantovani, Giovanna

2023

Overview

Abstract Background Pseudohypoparathyroidism (PHP) and related disorders newly referred to as inactivating PTH/PTHrP signaling disorders (iPPSD) are rare endocrine diseases. Many clinical features including obesity, neurocognitive impairment, brachydactyly, short stature, parathyroid hormone (PTH) resistance, and resistance to other hormones such as thyroid-stimulating hormone (TSH) have been well described, yet they refer mainly to the full development of the disease during late childhood and adulthood. Objective A significant delay in diagnosis has been reported; therefore, our objective is to increase awareness on neonatal and early infancy presentation of the diseases. To do so, we analyzed a large cohort of iPPSD/PHP patients. Methods We included 136 patients diagnosed with iPPSD/PHP. We retrospectively collected data on birth and investigated the rate of neonatal complications occurring in each iPPSD/PHP category within the first month of life. Results Overall 36% of patients presented at least one neonatal complication, far more than the general population; when considering only the patients with iPPSD2/PHP1A, it reached 47% of the patients. Neonatal hypoglycemia and transient respiratory distress appeared significantly frequent in this latter group, ie, 10.5% and 18.4%, respectively. The presence of neonatal features was associated with earlier resistance to TSH (P < 0.001) and with the development of neurocognitive impairment (P = 0.02) or constipation (P = 0.04) later in life. Conclusion Our findings suggest that iPPSD/PHP and especially iPPSD2/PHP1A newborns require specific care at birth because of an increased risk of neonatal complications. These complications may predict a more severe course of the disease; however, they are unspecific which likely explains the diagnostic delay.

• Publisher: Oxford University Press,Endocrine Society
• Subject: Brachydactyly / Children / Clinical / Cognition / Constipation / Disease / Diseases / Endocrine disorders / Endocrinology / Endocrinology and metabolism / Gestational age / Health aspects / Human health and pathology / Hypocalcemia / Hypoglycemia / Infants (Newborn) / Life Sciences / Mutation / Neonates / Neonatology / Obesity / Parathyroid hormone / Parathyroid hormone-related protein / Proteins / Pseudohypoparathyroidism / Signal transduction / Thyroid gland / Thyroid-stimulating hormone / Thyrotropin