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Frontiers in Endocrinology 2024Prader-Willi syndrome (PWS) is a rare disease, which shows a peculiar clinical phenotype, including obesity, which is different from essential obesity (EOB).... (Comparative Study)
Comparative Study
INTRODUCTION
Prader-Willi syndrome (PWS) is a rare disease, which shows a peculiar clinical phenotype, including obesity, which is different from essential obesity (EOB). Metabolomics might represent a valuable tool to reveal the biochemical mechanisms/pathways underlying clinical differences between PWS and EOB. The aim of the present (case-control, retrospective) study was to determine the metabolomic profile that characterizes PWS compared to EOB.
METHODS
A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to measure a total of 188 endogenous metabolites in plasma samples of 32 patients with PWS (F/M = 23/9; age: 31.6 ± 9.2 years; body mass index [BMI]: 42.1 ± 7.0 kg/m), compared to a sex-, age- and BMI-matched group of patients with EOB (F/M = 23/9; age: 31.4 ± 6.9 years; BMI: 43.5 ± 3.5 kg/m).
RESULTS
Body composition in PWS was different when compared to EOB, with increased fat mass and decreased fat-free mass. Glycemia and HDL cholesterol were higher in patients with PWS than in those with EOB, while insulinemia was lower, as well as heart rate. Resting energy expenditure was lower in the group with PWS than in the one with EOB, a difference that was missed after fat-free mass correction. Carrying out a series of Tobit multivariable linear regressions, adjusted for sex, diastolic blood pressure, and C reactive protein, a total of 28 metabolites was found to be associated with PWS (vs. non-PWS, i.e., EOB), including 9 phosphatidylcholines (PCs) ae, 5 PCs aa, all PCs aa, 7 lysoPCs a, all lysoPCs, 4 acetylcarnitines, and 1 sphingomyelin, all of which were higher in PWS than EOB.
CONCLUSIONS
PWS exhibits a specific metabolomic profile when compared to EOB, suggesting a different regulation of some biochemical pathways, fundamentally related to lipid metabolism.
Topics: Humans; Prader-Willi Syndrome; Female; Male; Adult; Metabolomics; Case-Control Studies; Retrospective Studies; Obesity, Morbid; Metabolome; Young Adult; Body Mass Index; Body Composition; Chromatography, Liquid; Tandem Mass Spectrometry
PubMed: 38812813
DOI: 10.3389/fendo.2024.1386265 -
Journal of Clinical Sleep Medicine :... Feb 2022Excessive daytime sleepiness is common in Prader-Willi syndrome (PWS), with prevalence ranging from 52% to 100%. The goal of this study was to establish the content...
STUDY OBJECTIVES
Excessive daytime sleepiness is common in Prader-Willi syndrome (PWS), with prevalence ranging from 52% to 100%. The goal of this study was to establish the content validity (ie, evidence that an instrument measures an intended concept of interest) of the parent/caregiver version of the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), a measure of daytime sleepiness, in PWS.
METHODS
Qualitative, dyadic semistructured video interviews were conducted with 18 caregivers and their children with PWS from April to June 2020. Concept elicitation and cognitive interview techniques were implemented. Thematic analyses allowed for examination of themes and data patterns.
RESULTS
All caregivers (mean age 49 years) were mothers of individuals with PWS who experienced troublesome daytime sleepiness (mean age 14 years). The most prevalent observable signs/symptoms of daytime sleepiness were sleepy/sleepiness (n = 17; 94.4%), tired/tiredness (n = 16; 88.9%), exhaustion/exhausted (n = 5; 27.8%), anxious/stressed (n = 5; 27.8%), irritable/frustrated (n = 5; 27.8%), having tantrums/outbursts (n = 5; 27.8%), and lethargy (n = 4; 22.2%). Daytime sleepiness impacted various aspects of health including mental, emotional, physical, and social well-being. When caregivers were asked about the activities associated with daytime sleepiness, all salient concepts elicited mapped to the ESS-CHAD; saturation was met after the first 4 interviews. Only 2 concepts, after physical exertion and while inactive/bored, did not map. Caregiver statements indicated that these concepts, although related to daytime activities, were atypical of daily routines. The ESS-CHAD was well understood and relevant to caregivers.
CONCLUSIONS
This study supports the content validity of the ESS-CHAD and its appropriateness for evaluating treatment efficacy of daytime sleepiness in PWS.
CITATION
Patel VP, Patroneva A, Glaze DG, Davis K, Merikle E, Revana A. Establishing the content validity of the Epworth Sleepiness Scale for Children and Adolescents in Prader-Willi syndrome. . 2022;18(2):485-496.
Topics: Adolescent; Anxiety; Caregivers; Child; Disorders of Excessive Somnolence; Humans; Middle Aged; Prader-Willi Syndrome; Sleepiness
PubMed: 34437052
DOI: 10.5664/jcsm.9632 -
Neuroscience and Biobehavioral Reviews Jan 2011Motor problems in Prader-Willi syndrome (PWS) are presumably related to abnormal body composition and certain neuromuscular abnormalities. The authors reviewed the... (Review)
Review
Motor problems in Prader-Willi syndrome (PWS) are presumably related to abnormal body composition and certain neuromuscular abnormalities. The authors reviewed the literature to evaluate the extent to which body composition is affected and gathered all findings on neuromuscular functioning in PWS. A systematic review was conducted in four databases (1956-2010). The methodological quality of each included article was evaluated. Thirty-eight papers were included: body composition (9 studies), neuromuscular functioning (7) and growth hormone (GH) effect studies (23). Increased fat mass and decreased lean body mass are characteristics of PWS. As a result, muscle mass is decreased by 25-37%, which might explain partly the weakness and hypotonia. However, there are also structural and functional muscle abnormalities, and cortical motor areas are hypo-excitable in PWS patients. Moreover, disuse as result of decreased activity in PWS could also contribute. GH treatment positively influences body composition, but does not normalize it. Training could prevent disuse and improves body composition. Therefore GH treatment and training will probably enhance one another.
Topics: Body Composition; Humans; Movement Disorders; Neuromuscular Junction; Prader-Willi Syndrome
PubMed: 21056055
DOI: 10.1016/j.neubiorev.2010.10.015 -
Journal of Medical Genetics Sep 2018Prader-Willi syndrome (PWS) is a complex genetic disorder associated with three different genetic subtypes: deletion of the paternal copy of 15q11-q13, maternal UPD for...
INTRODUCTION
Prader-Willi syndrome (PWS) is a complex genetic disorder associated with three different genetic subtypes: deletion of the paternal copy of 15q11-q13, maternal UPD for chromosome 15 and imprinting defect. Patients are typically diagnosed because of neonatal hypotonia, dysmorphism and feeding difficulties; however, data on the prenatal features of PWS are limited.
OBJECTIVE
The aim of the study was to identify and compare frequencies of prenatal and neonatal clinical features of PWS among the three genetic subtypes.
METHODS
Data from 355 patients with PWS from the Rare Diseases Clinical Research Network PWS registry were used to analyse multiple maternal and neonatal factors collected during an 8-year multisite study.
RESULTS
Among our cohort of 355 patients with PWS (61% deletion, 36% UPD and 3% imprinting defect) 54% were born by caesarean section, 26% were born prematurely and 34% with a low birth weight (frequencies 32%, 9.6% and 8.1%, respectively, in the general population). Fetal movements were reported as decreased in 72%. All babies were hypotonic, and 99% had feeding difficulties. Low Apgar scores (<7) were noted in 17.7% and 5.6% of patients, respectively, compared with 1% and 1.4%, respectively, in the general population. Maternal age and pre-pregnancy weight were significantly higher in the UPD group (p=0.01 and <0.001, respectively).
CONCLUSION
We found a higher rate of perinatal complications in PWS syndrome compared with the general population. No significant differences in the genetic subtypes were noted except for a higher maternal age and pre-pregnancy weight in the UPD subgroup.
Topics: Age Factors; Apgar Score; Body Weight; Cesarean Section; Female; Humans; Infant, Newborn; Infant, Premature; Prader-Willi Syndrome; Pregnancy; Pregnancy Outcome; Prognosis
PubMed: 29776967
DOI: 10.1136/jmedgenet-2017-105118 -
Human Brain Mapping Aug 2017Prader-Willi syndrome (PWS) is a genetic imprinting disorder that is mainly characterized by hyperphagia and childhood obesity. Previous neuroimaging studies revealed...
Prader-Willi syndrome (PWS) is a genetic imprinting disorder that is mainly characterized by hyperphagia and childhood obesity. Previous neuroimaging studies revealed that there is a significant difference in brain activation patterns between obese children with and without PWS. However, whether there are differences in the brain structure of obese children with and without PWS remains elusive. In the current study, we used T1-weighted and diffusion tensor magnetic resonance imaging to investigate alterations in the brain structure, such as the cortical volume and white matter integrity, in relation to this eating disorder in 12 children with PWS, 18 obese children without PWS (OB) and 18 healthy controls. Compared with the controls, both the PWS and OB groups exhibited alterations in cortical volume, with similar deficit patterns in 10 co-varying brain regions in the bilateral dorsolateral and medial prefrontal cortices, right anterior cingulate cortex, and bilateral temporal lobe. The white matter integrities of the above regions were then examined with an analysis method based on probabilistic tractography. The PWS group exhibited distinct changes in the reduced fractional anisotropy of white matter fibers connected to the co-varying regions, whereas the OB group did not. Our findings indicated that PWS and OB share similar gray matter alterations that are responsible for the development of eating disorders. Additionally, the distinct white matter alterations might explain the symptoms associated with food intake in PWS, including excessive hyperphagia and constant hunger. Hum Brain Mapp 38:4228-4238, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Age Factors; Brain; Child; Diffusion Tensor Imaging; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Neural Pathways; Obesity; Organ Size; Prader-Willi Syndrome; Sex Factors; White Matter
PubMed: 28543989
DOI: 10.1002/hbm.23660 -
Revista de Neurologia Feb 2006In recent years, Prader-Willi syndrome (PWS) has been conceptualised as being included within the autistic spectrum (AS). (Review)
Review
INTRODUCTION
In recent years, Prader-Willi syndrome (PWS) has been conceptualised as being included within the autistic spectrum (AS).
DEVELOPMENT
In this article, we review the studies that prove this to be the case, on the basis of both genetic and clinical evidence, and we also compare the core aspects that are found in the definition of AS and which are shared by PWS.
CONCLUSIONS
The article also reports the findings of a study conducted in the Valencian Region (Spain) and outlines a programme of therapy adapted to the different scores obtained on the AS inventory (IDEA).
Topics: Adolescent; Adult; Autistic Disorder; Child; Child, Preschool; Humans; Prader-Willi Syndrome
PubMed: 16555223
DOI: No ID Found -
European Journal of Medical Genetics Jan 2022Prader-Willi Syndrome (PWS) is a multi-system genetically determined neurodevelopmental disorder and the commonest cause of syndromal obesity. The development of... (Meta-Analysis)
Meta-Analysis
Prader-Willi Syndrome (PWS) is a multi-system genetically determined neurodevelopmental disorder and the commonest cause of syndromal obesity. The development of hyperphagia in early childhood is part of the phenotype arising as a result of an impaired neural response to food intake and the inability to regulate food intake in line with energy needs. Severe obesity develops if access to food is not controlled. In this review we evaluate the evidence for increased morbidity and mortality in PWS in order to establish the extent to which it is directly related to the obesity; a consequence of the eating behaviour itself independent of obesity; or associated with other characteristics of the syndrome. Medline, Cochrane, PsychINFO, CINAHL, Web of Science and Scopus databases were used to systematically identify published material on PWS and hyperphagia and syndrome-related morbidity and mortality. One hundred and ten key papers were selected. Data on 500 people with PWS indicated that the average age of death was 21 years and obesity was, as expected, a significant factor. However, the behaviour of hyperphagia itself, independent of obesity, was also important, associated with choking, gastric rupture, and/or respiratory illness. Other syndrome-related factors increased the risk for, and seriousness of, co-morbid illness or accidents. We conclude that improving life-expectancy largely depends on managing the immediate non-obesity and obesity-related consequences of the hyperphagia, through improved support. The development of new treatments that significantly reduce the drive to eat are likely to decrease morbidity and mortality improving quality of life and life expectancy.
Topics: Humans; Hyperphagia; Morbidity; Prader-Willi Syndrome
PubMed: 34748997
DOI: 10.1016/j.ejmg.2021.104379 -
BMC Pediatrics Feb 2024Prader-Willi syndrome (PWS) is a rare genetic disease often associated with bone problems, mainly scoliosis and hip dysplasia (HD). This study aimed to analyze the...
BACKGROUND
Prader-Willi syndrome (PWS) is a rare genetic disease often associated with bone problems, mainly scoliosis and hip dysplasia (HD). This study aimed to analyze the clinical characteristics of orthopedic deformities in patients with PWS.
METHODS
A retrospective study was conducted on 175 patients up to March 2023. The Cobb angle(CA) of the spine, the alpha angle of the hip joint, and the acetabular index (AI) were measured. This study aimed to evaluate the relationship between demographic parameters and bone deformities.
RESULTS
Scoliosis was found in 66 patients (43.7%), including 52 (78.8%) with mild scoliosis, 10 (15.2%) with moderate scoliosis, and 4 (6.1%) with severe scoliosis. Only seven patients received orthopedic treatment (10.6%). The median age of scoliosis was 4.5 years old, and the prevalence of scoliosis increased rapidly at the age of 5 years and adolescence. The mean CA in this study increased gradually with age. HD was found in 47 patients (38.2%), and 6 patients received orthopedic treatment (12.7%). The median age at HD was 1.8 years old. The mean AI of the study population decreased with age. The prevalence of HD treated with recombinant human growth hormone (rhGH) was low. No significant differences were observed in sex, genotype, body mass index (BMI), obesity rate, or onset of scoliosis and HD.
CONCLUSION
The prevalence of scoliosis and HD was higher in patients with PWS. The onset age and developmental trends of the different skeletal malformations were different. Early diagnosis and treatment are important for the prognosis and treatment of orthopedic diseases in patients with PWS.
Topics: Child; Adolescent; Humans; Child, Preschool; Infant; Prader-Willi Syndrome; Scoliosis; Retrospective Studies; Human Growth Hormone; Obesity
PubMed: 38355440
DOI: 10.1186/s12887-024-04603-7 -
Journal of Endocrinological... Oct 2021Prader-Willi syndrome (PWS) is associated to distinctive clinical symptoms, including obesity, cognitive and behavioral disorders, and bone impairment. Irisin is a...
BACKGROUND
Prader-Willi syndrome (PWS) is associated to distinctive clinical symptoms, including obesity, cognitive and behavioral disorders, and bone impairment. Irisin is a myokine that acts on several target organs including brain adipose tissue and bone. The present study was finalized to explore circulating levels of irisin in children and adult PWS patients.
METHODS
Seventy-eight subjects with PWS, 26 children (15 females, mean age 9.48 ± 3.6 years) and 52 adults (30 females, mean age 30.6 ± 10.7) were enrolled. Irisin serum levels were measured in patients and controls. Its levels were related with anthropometric and metabolic parameters, cognitive performance and bone mineral density either in pediatric or adult PWS. Multiple regression analysis was also performed.
RESULTS
Irisin serum levels in PWS patients did not show different compared with controls. A more in-depth analysis showed that both pediatric and adult PWS with DEL15 displayed significantly reduced irisin levels compared to controls. Otherwise, no differences in irisin concentration were found in UPD15 patients with respect to controls. Our study revealed that in pediatric PWS the 25(OH) vitamin-D levels affected irisin serum concentration. Indeed, patients who were not supplemented with vitamin D showed lower irisin levels than controls and patients performing the supplementation. Multiple regression analysis showed that irisin levels in pediatric and adult PWS were predicted by the genetic background and 25(OH)-vitamin D levels, whereas in a group of 29 adult PWS also by intelligent quotient.
CONCLUSION
We demonstrated the possible role of genetic background and vitamin-D supplementation on irisin serum levels in PWS patients.
Topics: Adult; Biomarkers; Case-Control Studies; Child; Dietary Supplements; Female; Fibronectins; Follow-Up Studies; Genetic Predisposition to Disease; Humans; Male; Prader-Willi Syndrome; Prognosis; Vitamin D; Vitamins
PubMed: 33656700
DOI: 10.1007/s40618-021-01533-4 -
Acta Neuropathologica Mar 2024Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of...
Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of cases. Two distinct genetic subtypes of PWS deletions are characterized, where type I (PWS T1) carries four extra haploinsufficient genes compared to type II (PWS T2). PWS T1 individuals display more pronounced physiological and cognitive abnormalities than PWS T2, yet the exact neuropathological mechanisms behind these differences remain unclear. Our study employed postmortem hypothalamic tissues from PWS T1 and T2 individuals, conducting transcriptomic analyses and cell-specific protein profiling in white matter, neurons, and glial cells to unravel the cellular and molecular basis of phenotypic severity in PWS sub-genotypes. In PWS T1, key pathways for cell structure, integrity, and neuronal communication are notably diminished, while glymphatic system activity is heightened compared to PWS T2. The microglial defect in PWS T1 appears to stem from gene haploinsufficiency, as global and myeloid-specific Cyfip1 haploinsufficiency in murine models demonstrated. Our findings emphasize microglial phagolysosome dysfunction and altered neural communication as crucial contributors to the severity of PWS T1's phenotype.
Topics: Humans; Mice; Animals; Prader-Willi Syndrome; Microglia; Carrier Proteins; Phenotype; Phagosomes; Adaptor Proteins, Signal Transducing
PubMed: 38556574
DOI: 10.1007/s00401-024-02714-0