ESPE Yearbook of Paediatric Endocrinology

In Brief: Clinical symptoms of Pseudohypoparathyroidism (PHP) and related disorders present during late childhood and adulthood. This study found that newborns with this group of conditions require specific care at birth due to increased risk of neonatal complications.

Commentary: Pseudohypoparathyroidism (PHP) and related disorders, newly referred to as inactivating PTH/PTHrP signalling disorders (iPPSD), are rare endocrine diseases. Their many clinical features include obesity, neurocognitive impairment, brachydactyly, short stature, parathyroid hormone (PTH) resistance, and resistance to other hormones such as thyroid-stimulating hormone (TSH). Full development of disease manifestations is mainly described during late childhood and adulthood, associated with significant delays in diagnosis.

This study analysed a large cohort of 136 iPPSD/PHP patients. Retrospective data from birth were collected to investigate the rate of neonatal complications occurring in each iPPSD/PHP category. 36% of patients had at least one neonatal complication, far more than the general population. This proportion was as high as 47% among patients with iPPSD2/PHP1A, including neonatal hypoglycemia (10.5%) and transient respiratory distress (18.4%). The presence of neonatal features was associated with earlier onset of TSH resistance (P<0.001) and with higher risk of neurocognitive impairment (P=0.02) and constipation (P=0.04) in later life.

These 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 nonspecific and, in the absence of positive family history, diagnostic delay remains likely.