Characterization of digestive manifestations in patients with impaired PTH/PTHrP signaling (iPPSD)/Pseudohypoparathyroidism.

Pseudohypoparathyroidism, newly classified as inactivating PTH/PTHrP signaling disorder (iPPSD) type 2 or type 3 is a rare disease caused by defects in the GNAS imprinted gene that encodes Gsα. The most common phenotype comprises resistance to hormones binding to G-protein coupled receptors such as PTH, PTHrP, or TSH, subcutaneous ossifications, short stature, brachydactyly, and early onset obesity. Uncommon features have been described including sleep apnea, asthma and resistance to calcitonin. We follow a large cohort of patients with iPPSD type 2 and type 3. Interestingly, digestive manifestations and in particular intractable constipation were regularly reported by families of children with iPPSD type 2 or type 3. Our study aimed to specify the frequency and characteristics of digestive manifestations in children followed up for iPPSD2 or iPPSD3 in our reference center. 36 patients aged between 2 and 18 years (32 followed up for iPPSD2 and 4 for iPPSD3) were included. Parents completed a specific questionnaire to assess any digestive disorders in their child. The diagnosis of constipation was established using the Bristol visual scale in the event of a score of less than 2 according to stool appearance. Parents reported constipation through the questionnaires in 22/36 (over 60% ) of the children. It was the most frequently reported digestive disorder. Among these 22 children, 19 (87%) had a Bristol score for stool shape and texture between 1 and 2 on a scale of 7, confirming constipation. Dedicated treatment had been initiated for 10 (55%) of them, yet only 3 families (16%) considered this treatment effective. Neonatal vomiting and eating disorders, such as lack of satiety or food selectivity, were also noted in 18 (50%) of patients, as was gastroesophageal reflux present in the neonatal period in 14 (40%) of children. There were no significant differences according to the type of iPPSD or patient age. Our work shows for the first time that digestive manifestations, including constipation, occur frequently in children followed for iPPSD, suggesting a potential role of Gsα and G protein receptors in the digestive tract. It is well known that constipation and digestive symptoms alter quality of life. Early management is therefore essential to improve the quality of life of children followed for iPPSD. Our data need to be confirmed on a larger cohort.

S. Karger AG, Basel.