Variability and change over time of weight and BMI among adolescents and adults with Prader-Willi syndrome: a 6-month text-based observational study

Abstract

Background: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder in which hyperphagia (excessive appetite) is a hallmark feature. Understanding how weight changes over time in this population is important for capturing the contemporary natural history of the disorder as well as assessing the impact of new treatments for hyperphagia. Therefore, we aimed to determine the feasibility of a remote assessment of weight change over time in PWS. Methods: We developed a text message-based, prospective cohort study of adolescents and adults with PWS to assess changes in weight and body mass index (BMI) over a six-month period. Weight was collected weekly, while changes in height, living situation, access to food, activity level, and medication were collected at three-month intervals. Results: One hundred and sixty-five participants enrolled in the study, with a mean age of 19.7 years (range 12-48). There was considerable variability in weight across participants (range: 76.8-207.7 kg). Thirty-three percent of the participants were normal weight, while 15% were overweight and 52% were obese. Overall, the weight of the study participants increased over the study period (mean weight change + 2.35%), while BMI was relatively stable, albeit high (mean BMI of 31.4 at baseline, mean BMI percent change + 1.42%). Changes in living situation, activity, food access, and medication had limited impact on weight and BMI changes. Multivariable analysis found that time, sex, age, and percentage of life on growth hormone (GH) therapy were statistically significant fixed effects. Participants submitted more than 95% of possible weight data points across the 26 weeks of the study. Conclusions: This remote, observational study of weight change in PWS showed small increases in weight and BMI over a six-month period. Participants were highly compliant with this text message-based study, suggesting that mobile technology-based data collection was manageable for the participants. We anticipate that the results of this study will inform clinical trials for hyperphagia/obesity related therapies in PWS and provide a basis for understanding the efficacy of new therapies for hyperphagia in the real-world setting.

Demographics and medical comorbidities among hospitalized patients with Prader–Willi Syndrome: A National Inpatient Sample analysis

“…Obesity codes were diagnosed during 230 (42.6%) of PWS hospitalizations, and 51.8% of hospitalizations involving individuals aged 4 or older. This is comparable to the 52% obesity rate found in a 6‐month observational study of 165 PWS patients in the United States (mean age 19.7 years; Vrana‐Diaz et al, 2020), and the 58.2% obesity rate in cross‐sectional study of 292 PWS adults in the United States (Dudley et al, 2008). These rates are higher than the prevalence of obesity in the general population, with 42.4% among US adults aged 20 and older being obese in 2018 (Fryar et al, 2020), and 16.1% of matched non‐PWS hospitalizations including a diagnosis of obesity.…”

Development of an International Database for a Rare Genetic Disorder: The MECP2 Duplication Database (MDBase)

“…Similarly, the research goal of the Global PWS Registry was to collect health-related data to better characterise and study the natural history of this disorder [ 28 ]. Research output stemming from the Global PWS Registry on issues such as weight problems, caregiver burden, suicidality, neuropsychiatric features, thrombosis risk and strabismus in PWS has been published, in the form of either retrospective studies from clinical and patient data collected via surveys (the largest of which featured data from 908 individuals) or prospective, observational studies recruiting individuals from the registry [ 30 , 31 , 32 , 33 , 34 , 35 ]. Such research output has been supported by funding from the Foundation for Prader–Willi Research [ 28 ].…”

DNA Damage in Prader Willi Syndrome Against Obesity

“…The NDN gene functions in axonal growth and regulates respiration rate. The recent discovery of genes, namely PWRN1 and PWRN2, located close to the NDN gene is believed to be the initial site for the complex activity of the SNURF SNRPN gene (10).…”

“…The mechanism of obesity in PWS is the condition of decreased plasma insulin and PYY, which results in loss of stimulation signals to POMC neurons and loss of inhibitory signals to NPY neurons in the arcuate nucleus, causing failure of α-MSH and β-MSH stimulation to control satiety through MCR4 activation in the paraventricular nucleus (19,20).…”

“…In children with PWS obtained abnormal fat distribution conditions, individuals with PWS have lower visceral adipose tissue than the subcutaneous adipose web; in terms of adipocyte proliferation and differentiation, there is a gene called the needed gene, in research it is said that overexpression of the required gene will inhibit adipogenesis, and downregulation of the gene will promote adipogenesis differentiation. In PWS, there is a condition of loss of expression of the needed gene in adipose tissue, which will cause insensitivity to lipolytic stimulation and accumulation of triglycerides (21,22). In children with PWS, there is a unique metabolic condition with low fasting insulin levels and improved insulin sensitivity.…”