Temple syndrome as a differential diagnosis to Prader-Willi syndrome: Identifying three new patients.

The two imprinting syndromes Temple syndrome (TS14) and Prader-Willi syndrome (PWS) share many features in infancy and childhood. TS14 is an important, yet often neglected, differential diagnosis to PWS. We wanted to assess the frequency of TS14 among patients tested for PWS. In all samples submitted to our lab for genetic PWS testing during 2014 and 2015, we consecutively conducted additional analyses for TS14. A total of 143 samples were included. The most frequent indications for testing were developmental delay, overweight, and hypotonia. For TS14 testing, we performed a methylation-sensitive MLPA-kit detecting deletions and methylation aberrations in chromosomal region 14q32. TS14 was confirmed in 3 out of 143 patients (2.1%). In comparison, PWS was also confirmed in three patients. Brief clinical descriptions of the TS14 patients are presented. Temple syndrome is presumably underdiagnosed, and should be considered when testing children for PWS.

Glucose homeostasis in adults with Prader-Willi syndrome during treatment with growth hormone: results from a 12-month prospective study.

OBJECTIVES: To investigate glucose homeostasis in relation to body mass index (BMI) in adults with PWS before and after GH therapy. DESIGN: We prospectively investigated the effects of a 12-month GH treatment on body composition and glucose homeostasis in relation to BMI in 39 adults, mean (±SD) age=28.6 (6.5) years with genetically verified PWS. We compared the results for different BMI categories (<25 kg/m²; 25-30 kg/m²; >30 kg/m²) and performed a regression analysis to detect predictors for homeostasis model of assessment-insulin resistance (HOMA-IR). RESULTS: The baseline HOMA-IR was higher, with BMI of >30 kg/m². Our main findings were as follows: i) GH treatment (mean final dose, 0.6 (0.25) mg) was associated with small increases in fasting p-glucose, 2-h p-glucose by oral glucose load tolerance test, HOMA-IR and lean mass, and a reduction in fat mass. ii) Whereas the baseline HOMA-IR was associated with increased BMI (>30 kg/m²), we found no differences in HOMA-IR among the BMI categories after 12 months of GH. iii) Stepwise linear regression identified the triglyceride level as the strongest predictor of HOMA-IR at baseline, whereas an increase in VAT was the strongest predictor of the increase in HOMA-IR after therapy. CONCLUSIONS: GH treatment for 12 months in adults with PWS resulted in an increase in HOMA-IR, irrespective of BMI, confirming that control of HbA1c is essential during GH treatment in PWS.

Growth hormone treatment in adults with Prader-Willi syndrome: the Scandinavian study.

Prader-Willi syndrome (PWS) is characterized by short stature, muscular hypotonia, cognitive dysfunction, and hyperphagia usually leading to severe obesity. Patients with PWS share similarities with growth hormone deficiency (GHD). Few studies have dealt with growth hormone (GH) treatment in PWS adults. The purpose of the Scandinavian study was to evaluate the effects of GH on body composition, lipid and glucose metabolism, physical performance and safety parameters in adults with PWS. Twenty-five women and 21 men with PWS were randomized to treatment with GH or placebo during 1 year followed by 2 years of open labeled GH treatment. At baseline 1/3 had normal BMI, six patients severe GHD, ten impaired glucose tolerance and seven diabetes. At 1 year insulin-like growth factor I (IGF-I) SDS had increased by 1.51 (P < 0.001) and body composition improved in the GH treated group. Visceral fat decreased by 22.9 ml (P = 0.004), abdominal subcutaneous fat by 70.9 ml (P = 0.003) and thigh fat by 21.3 ml (P = 0.013), whereas thigh muscle increased 6.0 ml (P = 0.005). Lean body mass increased 2.25 kg (P = 0.005), and total fat mass decreased 4.20 kg (P < 0.001). The positive effects on body composition were maintained after 2 years of GH treatment. Peak expiratory flow increased by 12% (P < 0.001) at 2 years of GH treatment. Lipid and glucose metabolism were unchanged, however, three patients developed diabetes at 2 years of GH treatment. In conclusion GH treatment had beneficial effects on the abnormal body composition without serious adverse events making it a logic treatment option in adults with PWS.

Growth hormone treatment for two years is safe and effective in adults with Prader-Willi syndrome.

OBJECTIVE: Prader-Willi syndrome (PWS) shares similarities with the growth hormone (GH) deficiency syndrome in regards to reduced lean body mass and increased fat mass and several short-term trials with GH treatment have demonstrated beneficial effects on body composition. The aim of the present study was to evaluate the effects and safety of two years of GH therapy in adults with PWS. DESIGN: Forty-three adults (24 women) with genetically verified PWS were included. Blood samples, body composition as measured by computed tomography (CT) and dual-energy x-ray absorptiometry (DXA) were performed at baseline and during two years of continued GH treatment. RESULTS: Thirty-nine patients completed treatment for two years. The GH dosage averaged 0.61 mg/day (range 0.2-1.6). Based upon CT, body composition improved at two years; thigh muscle volume increased 6.7 mL (3.7 to 9.7; P<0.001) whereas abdominal subcutaneous fat volume decreased by 53.3 mL (13.8 to 92.9; P=0.01). By DXA, lean body mass improved 2.8 kg (1.9 to 3.6; P<0.001), whereas fat mass decreased by 3.0 kg (1.1 to 4.8; P=0.003). Lung function as evaluated by peak expiratory flow increased 12% (p<0.001) - indicating improved muscle function. Adverse effects were few. Fifteen out of 39 patients had diabetes (DM; n=4) or impaired glucose tolerance (IGT; n=11) prior to GH treatment. Among the 11 patients with IGT, three reverted to normal glucose tolerance, while three progressed to overt DM at two years of GH treatment. CONCLUSION: The known beneficial effects of GH treatment upon body composition in PWS are maintained during two years continuous treatment. With appropriate control, GH is a safe treatment option in adults with PWS.

One year of growth hormone treatment in adults with Prader-Willi syndrome improves body composition: results from a randomized, placebo-controlled study.

CONTEXT: Prader-Willi syndrome (PWS) is a multisymptomatic disease that shares many similarities with the GH deficiency syndrome, including altered body composition with more body fat than lean body mass. OBJECTIVE: Our objective was to investigate the effect of GH on body composition in adults with PWS. DESIGN AND PATIENTS: Forty-six adults with PWS were randomized to GH or placebo treatment for 12 months in a double-blind trial. MAIN OUTCOME MEASURES: We evaluated change in regional body composition of the abdomen and thigh as measured by computed tomography and change in total body composition as measured by dual-energy x-ray absorptiometry. RESULTS: Forty patients completed the study. Baseline median IGF-I sd score was -0.4. GH treatment increased IGF-I by 125 µg/liter (1.51 sd score), and based upon computed tomography, body composition improved with a decrease in visceral fat mass of 22.9 ml (P = 0.004), abdominal sc fat mass 70.9 ml (P = 0.003), and thigh fat mass 21.3 ml (P = 0.013), whereas thigh muscle mass increased 6.0 ml (P = 0.005). By dual-energy x-ray absorptiometry, lean body mass improved 2.25 kg (P = 0.005), and total fat mass decreased 4.20 kg (P < 0.001). No major side effects were seen. CONCLUSION: Unrelated to the GH-IGF-I levels at baseline, our results showed that long-term treatment with GH effectively improved body composition and represents a safe, potential treatment option, relieving some of the negative consequences of PWS.

Body composition, endocrine and metabolic profiles in adults with Prader-Willi syndrome.

OBJECTIVE: Prader-Willi syndrome (PWS) is a complex genetic disease associated with hypothalamic-pituitary dysfunction and severe obesity. The aim of the present study was to describe the relationships between body composition, metabolic and hormonal profiles in PWS adults. METHOD: Forty six adults with genetically verified PWS, 25 women and 21 men, median age 28 years were studied. Body composition was evaluated by standard anthropometric procedures and with computed tomography (CT) of the abdomen and at the mid-femur level. CT of abdomen was compared to 22 healthy, unmatched adults. Circulating lipids were measured and oral glucose tolerance test (OGTT) and hormonal screening including GH secretory capacity (GHRH/arginine test) was carried out. RESULTS: Median body mass index (BMI) was 27.2 kg/m(2), with women being more obese than men. Sixteen patients had dyslipidaemia, 10 impaired glucose tolerance and seven had diabetes. Fifty percent were hypogonadal and six fulfilled BMI related criteria for growth hormone deficiency (GHD). Visceral to subcutaneous abdominal fat ratio was reduced in PWS. Visceral abdominal fat fraction correlated with both subcutaneous fat, BMI and peak GH-response. Thigh muscle volume was about half of the thigh fat volume. Beneficial effects of sex-steroid replacement on body composition were not observed. CONCLUSIONS: Body fat was primarily located subcutaneously and metabolic consequences of obesity limited. The abnormal body composition similar to that in non-PWS GHD adults increases the interest of GH treatment in the prevention of obesity in adults with PWS.

Assessment of physical function in adults with Prader-Willi syndrome.

PURPOSE: To evaluate implementation of at test battery for assessing physical function in adults with Prader-Willi syndrome (PWS). METHOD: Forty-three adults with PWS, 20 men and 23 women, mean age 29 +/- 9 years. Body mass index (BMI) and body composition were measured. A test battery a.m. Guralnik for standing balance, 2.4 m and 10 m walk and repeated rising from a chair was scored and evaluated. RESULTS: Mean BMI was 29.4 +/- 9.1 kg/m(2), body fat mass (FM) 26.0 +/- 16.1 kg. The adults with PWS managed the test battery well, and high scores were achieved for standing balance and 2.4 m walk. In contrast, only 13 managed maximum score in the repeated rising from a chair and 31 to walk 10 m for 6 s or faster. Significant correlations were seen between 2.4 m walk and FM ( p = 0.041) and between 10 m walk and BMI ( p = 0.001) and FM ( p = 0.019). CONCLUSIONS: Repeated rising from a chair and 10 m walk are useful assessments in clinical practice to identify adults with PWS with reduced physical function. Reduced performance was related to higher BMI and FM emphasising the importance of efforts to keep normal body weight and body composition in adults with PWS. These measures might be useful in monitoring effects of intervention.