Energy expenditure in obese children with pseudohypoparathyroidism type 1a

Abstract

ContextPatients with pseudohypoparathyroidism type 1a (PHP-1a) develop early-onset obesity. The abnormality in energy expenditure and/or energy intake responsible for this weight gain is unknown.ObjectiveThe aim of this study was to evaluate energy expenditure in children with PHP-1a compared with obese controls.PatientsWe studied 6 obese females with PHP-1a and 17 obese female controls. Patients were recruited from a single academic center.MeasurementsResting energy expenditure and thermogenic effect of a high fat meal were measured using whole room indirect calorimetry. Body composition was assessed using whole body dual energy x-ray absorptiometry. Fasting glucose, insulin and hemoglobin A1C were measured.ResultsChildren with PHP-1a had decreased resting energy expenditure compared with obese controls (P <0.01). After adjustment for fat free mass, the PHP-1a group’s resting energy expenditure was 346.4 kcals/day less than obese controls (95% CI [−585.5 to −106.9], P <0.01). The thermogenic effect of food, expressed as percent increase in postprandial energy expenditure over resting energy expenditure, was lower in PHP-1a patients than obese controls but did not reach statistical significance (absolute reduction of 5.9%, 95% CI [−12.2% to 0.3%], P = 0.06).ConclusionsOur data indicate that children with PHP-1a have decreased resting energy expenditure compared with obese controls and that may contribute to the development of obesity in these children. These patients may also have abnormal diet-induced thermogenesis in response to a high fat meal. Understanding the causes of obesity in PHP-1a may allow for targeted nutritional or pharmacologic treatments in the future.

From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network

“…Growth hormone deficiency, impaired lipolytic response of adrenaline (101) or decreased resting energy expenditure (106) contribute to the development of obesity in patients with mutations on the maternal allele of GNAS (23,107). Obesity is also a frequent feature in patients affected with acrodysostosis (16,90,108).…”

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international consensus statement

“…Children with PHP1A and obesity show both decreased resting energy expenditure compared with controls with obesity and hyperphagic symptoms similar to those seen in BMI-matched controls with obesity 39,111,112 . In older (late infancy, adolescence and young adulthood) patients, this hyperphagic trait seems to abate 111 , and energy expenditure seems to improve to low-normal 113 .…”

“…In brief, PHP1A is caused by inactivating variants on the maternal allele of the GNAS gene within exons 1-13 (referring sequences NG_016194.1/NM_001077488.1 and LRG_1051), including both point mutations and rare gene rearrangements 16,23,27,41,45,86,88,97,112,122,[143][144][145][146][147][148] ( Supplementary Fig. 1b).…”

Molecular and Clinical Aspects of Pseudohypoparathyroidism

“…172 However, meal-induced thermogenesis, a response believed to require central melanocortin activation, tended to be lower in these adult PHP type 1a patients, 172 similar to what has been observed in children with PHP type 1a. 173 By contrast, two other studies performed in children with PHP type 1a showed a profound reduction in serum norepinephrine 174 or lower resting energy expenditure 173 as compared with obese controls. Taken in context, these studies imply that metabolic differences may be more significant in children than in adults with PHP type 1a, and are consistent with the observation that the obesity in PHP type 1a is more severe in the pediatric than in the adult population.…”