Dataset Information

Energy expenditure in obese children with pseudohypoparathyroidism type 1a.

ABSTRACT:

Context

Patients 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.

Objective

The aim of this study was to evaluate energy expenditure in children with PHP-1a compared with obese controls.

Patients

We studied 6 obese females with PHP-1a and 17 obese female controls. Patients were recruited from a single academic center.

Measurements

Resting energy expenditure (REE) 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.

Results

Children with PHP-1a had decreased REE compared with obese controls (P<0.01). After adjustment for fat-free mass, the PHP-1a group's REE was 346.4 kcals day(-1) less than obese controls (95% CI (-585.5--106.9), P<0.01). The thermogenic effect of food (TEF), expressed as percent increase in postprandial energy expenditure over REE, was lower in PHP-1a patients than obese controls, but did not reach statistical significance (absolute reduction of 5.9%, 95% CI (-12.2-0.3%), P=0.06).

Conclusions

Our data indicate that children with PHP-1a have decreased REE compared with the 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.

SUBMITTER: Shoemaker AH

PROVIDER: S-EPMC3610772 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Energy expenditure in obese children with pseudohypoparathyroidism type 1a.

Shoemaker A H AH Lomenick J P JP Saville B R BR Wang W W Buchowski M S MS Cone R D RD

International journal of obesity (2005) 20121211 8

<h4>Context</h4>Patients 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.<h4>Objective</h4>The aim of this study was to evaluate energy expenditure in children with PHP-1a compared with obese controls.<h4>Patients</h4>We studied 6 obese females with PHP-1a and 17 obese female controls. Patients were recruited from a single academic center.<h4>Measurements</h4>Resting ...[more]

PMID: 23229731

Similar Datasets

Project description:BackgroundAlbright hereditary osteodystrophy (AHO) is caused by heterozygous inactivating mutations in GNAS. Patients with maternally-inherited mutations develop pseudohypoparathyroidism type 1A (PHP1A) with multi-hormone resistance and aberrant craniofacial and skeletal development among other abnormalities. Chiari malformation type 1 (CM1), a condition in which brain tissue extends into the spinal canal when the skull is too small, has been reported in isolated cases of PHP1A. It has been hypothesized to be associated with growth hormone (GH) deficiency. Given the adverse clinical sequelae that can occur if CM1 goes unrecognized, we investigated the previously undetermined prevalence of CM1, as well as any potential correlations with GH status, given the known increased prevalence of GH deficiency in PHP1A. We also investigated these metrics for low lying cerebellar tonsils (LLCT), defined as tonsillar descent less than 5 mm below the foramen magnum. In addition, we investigated possible correlations of CM1/LLCT with advanced hand/wrist bone ages and craniofacial abnormalities known to occur in PHP1A to determine whether premature chondrocyte differentiation and/or aberrant craniofacial development could be potential etiologies of CM1/LLCT through both human studies and investigations of our AHO mouse model.MethodsWe examined patients with PHP1A in our clinic and noticed CM1 more frequently than expected. Therefore, we set out to determine the true prevalence of CM1 and LLCT in a cohort of 54 mutation-confirmed PHP1A participants who had clinically-indicated brain imaging. We examined potential correlations with GH status, clinical features, biological sex, genotype, and hand/wrist bone age determinations. In addition, we investigated the craniofacial development in our mouse model of AHO (Gnas E1+/-m) by histologic analyses, dynamic histomorphometry, and micro-computerized tomographic imaging (MCT) in order to determine potential etiologies of CM1/LLCT in PHP1A.ResultsIn our cohort of PHP1A, the prevalence of CM1 is 10.8%, which is at least 10-fold higher than in the general population. If LLCT is included, the prevalence increases to 21.7%. We found no correlation with GH status, biological sex, genotype, or hand/wrist bone age. Through investigations of our Gnas E1+/-m mice, the correlate to PHP1A, we identified a smaller cranial vault and increased cranial dome angle with evidence of hyperostosis due to increased osteogenesis. We also demonstrated that there was premature closure of the spheno-occipital synchondrosis (SOS), a cartilaginous structure essential to the development of the cranial base. These findings lead to craniofacial abnormalities and could contribute to CM1 and LLCT development in PHP1A.ConclusionThe prevalence of CM1 is at least 10-fold higher in PHP1A compared to the general population and 20-fold higher when including LLCT. This is independent of the GH deficiency that is found in approximately two-thirds of patients with PHP1A. In light of potential serious consequences of CM1, clinicians should have a low threshold for brain imaging. Investigations of our AHO mouse model revealed aberrant cranial formation including a smaller cranium, increased cranial dome angle, hyperostosis, and premature SOS closure rates, providing a potential etiology for the increased prevalence of CM1 and LLCT in PHP1A.

Dataset Information

Energy expenditure in obese children with pseudohypoparathyroidism type 1a.

Context

Objective

Patients

Measurements

Results

Conclusions

Publications

Energy expenditure in obese children with pseudohypoparathyroidism type 1a.

Similar Datasets

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