Metabolic responses to walking in children with Prader‐Willi syndrome on growth hormone replacement therapy

To the Editor: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder that results from a lack of expression of genes on the paternal chromosome 15q11.2-q13 region. PWS is characterized by hypotonia, low lean mass, increased fat mass, growth hormone deficiency, hyperphagia, and can lead to morbid obesity (Cassidy, Schwartz, Miller, & Driscoll, 2012). Previous studies have shown that energy expenditure (EE) and metabolic activity were lower during rest and spontaneous activity in PWS compared to people without PWS (Alsaif et al., 2017; Bekx, Carrel, Shriver, Li, & Allen, 2003; Butler, Theodoro, Bittel, & Donnelly, 2007; Lloret-Linares et al., 2013; Schoeller, Levitsky, Bandini, Dietz, & Walczak, 1988; van Mil et al., 2000). However, EE in PWS has not been directly measured during exercise. Increased fatness has been linked with metabolic inflexibility during exercise and decreased ability for fat oxidation and weight regulation (Aucouturier, Duche, & Timmons, 2011). Previously, two studies have suggested lower fat oxidation in adults with PWS during an 8 hr period (Butler et al., 2007) and after exercise in youth with PWS (Rubin et al., 2017) compared to controls. However, after submaximal cycling no differences were observed in fat oxidation between PWS and controls (Rubin et al., 2015). While all three studies supported normal glucose oxidation, none evaluated substrate utilization during exercise. As for those without PWS (Goran, Reynolds, & Lindquist, 1999), regular exercise is crucial for the management of a healthy body mass in PWS (Cassidy et al., 2012). Knowing the caloric cost of a commonly reported exercise mode in PWS, such as walking (Rubin, Weiss, Mouttapa, & Barrera-Ng, 2012), can help tailor exercise regimens to manage body weight. Our study reports on the metabolic cost and substrate utilization during walking in children with PWS in comparison to controls with and without nonsyndromal obesity (NSO). Nine children with PWS documented through Chromosomes, FISH 15, DNA methylation and/or DNA polymorphism studies participated. Diagnoses included deletion (n = 4), uniparental maternal disomy (n = 4), and unknown with either uniparental maternal disomy or imprinting defect (n = 1). Eight of nine children with PWS had been on growth hormone replacement therapy (GHRT) for more than 2 years at the time of the study; dosages ranged from 0.3 mg day to 2.0 mg day. Additionally, two children with PWS were on thyroid hormone treatment for hypothyroidism. Nine children of normal weight (NW) and nine with NSO served as controls. NW was defined as having a body mass index (BMI) lower than the 85th percentile for age and sex (%). NSO was defined as having a BMI greater than or equal to the 95th percentile. Written assent and consent forms were signed by participants and their parent before participation. Forms were approved by the Institutional Review Board at California State University, Fullerton, CA. Participants reported to the laboratory after a minimum of 2 hr fast and no exercise for at least 24 hr. The participant’s parents completed a medical and exercise history form to screen for any potential health risks and contraindications to exercise. Afterward, measurements collected included: anthropometrics, body composition, exercise HR, walking EE (WEE), and substrate utilization (fat and carbohydrate). Body mass was obtained using a digital scale (ES200L; Ohaus, Pine Brook, NJ), with the participants wearing a t-shirt, shorts, and no shoes. Stature was measured at the end of inhalation against a wallmounted stadiometer (Seca, Ontario, CA). BMI was computed dividing body mass (kg) by the stature (m). BMI percentile was calculated using the Centers for Disease Control and Prevention online calculator for child and teen. Heart rate (HR) was measured via telemetry (Polar, Lake Success, NY). Body composition (total body fat [TBF] and lean body mass [LBM]) was measured with a dual-energy X-ray Received: 13 March 2018 Revised: 17 July 2018 Accepted: 19 July 2018