ESPE Abstracts

Introduction: Pseudohypoparathyroidism (hereafter named iPPSD for inactivating PTH/PTHrP Disorder) is a rare disease characterized by hormonal resistance including PTH, subcutaneous ossifications, short stature, brachymetacarpy and early onset obesity. iPPSD type 2 and 3 are caused by genetic or epigenetic variations in the GNAS gene or its promoters. Although uncommon features have been identified such as severe asthma or sleep apnea, digestive manifestations have been poorly addressed in the literature. However, in the clinical practice for the follow-up of a large cohort iPPSD at the French reference center for rare diseases of calcium and phosphate metabolism (CRMR CaP), relatives of children and affected children frequently reported digestive manifestations and especially severe constipation.

Objective: To precise the incidence and characteristics of digestive manifestations in children with iPPSD2 or iPPSD3.

Material and Method: We included 36 patients aged between 2 and 18 years with iPPSD (iPPSD2 n=32; iPPSD3 n=4) followed at the CRMR CaP. Each family filled in a specific questionnaire to assess the presence of digestive symptoms in their children including constipation, feeding difficulties or vomiting. The Bristol visual scale was used to confirm the existence of constipation.

Results: Constipation was the most frequently reported feature, present in more than 60% of the children (n=22/36 children). More than 80% of these 22 children had a Bristol score between 1 and 2, confirming constipation. Specific treatment had had been already administered in 55% of them but only 3 families (14%) considered this treatment effective. Neonatal vomiting and eating disorders, such as lack of satiety or food selectivity, were also observed in 50% of patients, as well as gastroesophageal reflux in the neonatal period in 40% of children. No significant difference was found according to the type of iPPSD or the age of the patients.

Conclusion: We report for the first time the high incidence of digestive manifestations and especially constipation in children with iPPSD. This is significantly higher than in healthy children where constipation is found in 10% of children. This suggests the potential dysfunction of GNAS and the G protein coupled receptors expressed in the digestive tract. Early adapted management of digestive manifestations and specifically constipation is essential to improve the quality of life for children with iPPSD, even if these data should be confirmed with a larger cohort.