The neutrophil to lymphocyte ratio (NLR) positively correlates with the presence and severity of metabolic syndrome in obese adults, but not in obese children/adolescents.

Metabolic syndrome (MetS) associated with obesity is a pathological condition increasing worldwide. Recent studies have demonstrated that the neutrophil to lymphocyte ratio (NLR) can be successfully used to stage MetS in obese adults. The aim of the study was to evaluate NLR values in 552 children/adolescents (M 219, F 333; 14.8 [12.9-16.3] years) and 231 adults (M 88, F 143; 52.3 [36.4-63.3] years) with morbid obesity, subdivided into subgroups according with the presence or absence of MetS. Adult patients with obesity showed a higher prevalence of MetS compared to the pediatric population (71% vs 26%), associated with a greater number of subjects with 3 and 4-5 altered components for MetS. NLR was higher (P-value = 0.041) in adults with MetS compared with those without. NLR values also positively correlated with the severity grade of the syndrome (P-value = 0.032). By contrast, in pediatric subjects with obesity with MetS, NLR values were comparable with those recorded in subjects without MetS (P-value = 0.861), no correlation being found with MetS severity (P-value = 0.441). Our study confirms the importance of NLR as an inflammatory indicator associated with MetS in adult subjects with severe obesity, while it excludes a similar role in children/adolescents.

Gait strategy and body composition in patients with Prader-Willi syndrome.

PURPOSE: Individuals with Prader-Willi syndrome (PWS) exhibit reduced lean body mass and increased fat-lean mass ratio when compared with individuals of normal weight and obese ones. Thus, research on the association of functional limitations during gait and body composition may be of great importance from a rehabilitative viewpoint. In particular, the aim of this study was to compare the gait profile of persons with PWS to that of unaffected individuals and to see if a relationship exists between gait profile and body composition in individuals with PWS. METHODS: Eighteen individuals with PWS and 20 unaffected individuals (Healthy Group: HG) were assessed. Their gait pattern was quantified with 3D-Gait Analysis (3D-GA). Overall body weight, lean and fat masses were measured by dual-energy X-ray absorptiometry. RESULTS: Individuals with PWS were found to be characterized by a significantly different (p < 0.05) gait pattern with respect to healthy controls in terms of both kinematic and kinetic parameters. No correlations were found between kinematic parameters and overall mass and lean/fat mass, while some parameters associated with ground reaction force were found to be significantly correlated with overall mass, lean mass and fat mass. Significant regression models were obtained, including impact and propulsive force and loading rate. CONCLUSION: Our data suggest that in individuals with PWS, gait is influenced by the overall and lean body mass. Thus, therapeutic strategies should target both weight reduction and lean mass increase to optimize gait, minimize articular stress, and reduce the risk of repetitive strain on the lower limbs. LEVEL OF EVIDENCE: Level III: Case-control analytic study.

Update on Diabetes Mellitus and Glucose Metabolism Alterations in Prader-Willi Syndrome.

PURPOSE OF REVIEW: This review summarizes our current knowledge on type 2 diabetes mellitus (T2DM) and glucose metabolism alterations in Prader-Willi syndrome (PWS), the most common syndromic cause of obesity, and serves as a guide for future research and current best practice. RECENT FINDINGS: Diabetes occurs in 10-25% of PWS patients, usually in adulthood. Severe obesity is a significant risk factor for developing of T2DM in PWS. Paradoxically, despite severe obesity, a relative hypoinsulinemia, without the expected insulin resistance, is frequently observed in PWS. The majority of PWS subjects with T2DM are asymptomatic and diabetes-related complications are infrequent. Long-term growth hormone therapy does not adversely influence glucose homeostasis in all ages, if weight gain does not occur. Early intervention to prevent obesity and the regular monitoring of glucose levels are recommended in PWS subjects. However, further studies are required to better understand the physiopathological mechanisms of T2DM in these patients.

Anthropometric characteristics of newborns with Prader-Willi syndrome.

This is a retrospective multicenter nationwide Italian study collecting neonatal anthropometric data of Caucasian subjects with Prader-Willi syndrome (PWS) born from 1988 to 2018. The aim of the study is to provide percentile charts for weight and length of singletons with PWS born between 36 and 42 gestational weeks. We collected the birth weight and birth length of 252 male and 244 female singleton live born infants with both parents of Italian origin and PWS genetically confirmed. Percentile smoothed curves of birth weight and length for gestational age were built through Cole's lambda, mu, sigma method. The data were compared to normal Italian standards. Newborns with PWS showed a lower mean birth weight, by 1/2 kg, and a shorter mean birth length, by 1 cm, than healthy neonates. Females with a 15q11-13 deletion were shorter than those with maternal uniparental maternal disomy of chromosome 15 (p < .0001). The present growth curves may be useful as further traits in supporting a suspicion of PWS in a newborn. Because impaired prenatal growth increases risk of health problems later in life, having neonatal anthropometric standards could be helpful to evaluate possible correlations between the presence or absence of small gestational age and some clinical and metabolic aspects of PWS.

Indexes of adiposity and body composition in the prediction of metabolic syndrome in obese children and adolescents: Which is the best?

BACKGROUND AND AIM: There is no agreement about which index of adiposity and/or body composition is the most accurate in identifying the metabolic syndrome (METS). The aim of our study was to compare the accuracy of the different indexes in order to recognize the most reliable. METHODS AND RESULTS: We evaluated 1332 obese children and adolescents (778 females and 554 males), aged 14.4 ± 1.8 yrs, Body Mass Index (BMI) standard deviation scores (SDS) 2.99 ± 0.55, followed at the Istituto Auxologico Italiano, a tertiary center for childhood obesity. For each subject the following indexes were assessed: BMI, BMI SDS, Fat-Free Mass Index (FFMI), Fat Mass Index (FMI), Tri-Ponderal Mass Index (TMI), Waist-to-Height ratio (WtHR) and a new one, the Body Mass Fat Index (BMFI), which normalizes the BMI for percentage of body fat and the waist circumference. Thereafter we calculated for each index a threshold value for age and sex, in order to compare their accuracy, sensitivity and specificity in identifying the METS. There was a good correlation among indexes (p < 0.0001 for all). However, when the area under the curve (AUC) was compared, some of them, in particular the BMFI and the BMI, performed better than the other ones, although the differences were small. CONCLUSIONS: BMI, which neither considers body composition nor fat distribution, performs as good as other indexes, and should therefore be the preferred one, also because of the easiness of its calculation.

Assessment of fat-free mass from bioelectrical impedance analysis in men and women with Prader-Willi syndrome: cross-sectional study.

We have recently shown that population-specific formulae are required to estimate fat-free mass (FFM) from bioelectrical impedance analysis (BIA) in obese women with Prader-Willi syndrome (PWS) matched by age and percent fat mass (FM) to non-PWS women. The present cross-sectional study was aimed at developing generalised BIA equations that could be used in PWS subjects independently of sex and FM. We used dual-energy X-ray absorptiometry to measure FFM and BIA to measure whole-body impedance at 50 kHz (Z50) in 34 women and 21 men with PWS. The impedance index, that is, height (cm)2/Z50 (Ω), explained 77% (BCa-bootstrapped 95% CI 65 to 85%) of the variance of FFM with a root mean squared error of the estimate of 3.7 kg (BCa-bootstrapped 95% CI 3.2 to 4.5 kg). BIA can be used to estimate FFM in obese and non-obese PWS men and women by means of population-specific equations.

Gait initiation and termination strategies in patients with Prader-Willi syndrome.

BACKGROUND: Gait Initiation (GI) is a functional task representing one of the first voluntary destabilizing behaviours observed in the development of a locomotor pattern as the whole body centre of mass transitions from a large to a small base of support. Conversely, Gait Termination (GT) consists in the transition from walking to standing which, in everyday life, is a very common movement. Compared to normal walking, it requires higher control of postural stability. For a safe GT, the forward movement of the body has to be slowed down to achieve a stable upright position. Stability requirements have to be fulfilled for safe GT. In individuals with Prader-Willi syndrome (PWS), excessive body weight negatively affects the movement, such as walking and posture, but there are no experimental studies about GI and GT in these individuals. The aim of this study was to quantitatively characterise the strategy of patients with PWS during GI and GT using parameters obtained by the Center of Pressure (CoP) track. METHODS: Twelve patients with PWS, 20 obese (OG) and 19 healthy individuals (HG) were tested using a force platform during the GI and GT tasks. CoP plots were divided into different phases, and duration, length and velocity of the CoP trace in these phases were calculated and compared for each task. RESULTS: As for GI, the results showed a significant reduction of the task duration and lower velocity and CoP length parameters in PWS, compared to OG and HG. In PWS, those parameters were reduced to a higher degree with respect to the OG. During GT, longer durations, similar to OG, were observed in PWS than HG. Velocity is reduced when compared to OG and HG, especially in medio-lateral direction and in the terminal part of GT. CONCLUSIONS: From these data, GI appears to be a demanding task in most of its sub-phases for PWS individuals, while GT seems to require caution only towards the end of the task. Breaking the cycle of gait into the phases of GI and GT and implementing specific exercises focusing on weight transfer and foot clearance during the transition phase from the steady condition to gait will possibly improve the effectiveness of rehabilitation and fall and injury prevention.

The rehabilitation of children and adolescents with severe or medically complicated obesity: an ISPED expert opinion document.

Severe/medically complicated obesity in childhood, and particularly in adolescence, is a real disability that requires an intensive and continuous approach which should follow the procedures and schedule of rehabilitation medicine. Given the lack of a specific document focusing on children and adolescents, the Childhood Obesity Study Group set out to explore the available evidence for the treatment of severe or medically complicated obesity and to set standards tailored to the specific context of the Italian Health Service. Through a series of meetings and electronic communications, the writing committee (selected from members of the Study Group) selected the key issues, explored the literature and produced a draft document which was submitted to the other experts until the final synthesis was approved by the group. In brief, the following issues were involved: (1) definition and epidemiology; (2) identification of common goals designed to regain functional competence and limit the progression of metabolic and psychological complications; (3) a multi-professional team approach; (4) the care setting. This paper is an expert opinion document on the rehabilitation of severe and medically complicated obesity in children and adolescents produced by experts belonging to the Childhood Obesity Study Group of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED).

Adults with Prader-Willi syndrome have weaker bones: effect of treatment with GH and sex steroids.

Obesity has been considered to have a protective effect against the risk of fractures in adults. However, a high frequency of fracture is described in obese adults with Prader-Willi syndrome. To evaluate bone geometry, density and strength in a group of adult obese patients with Prader-Willi syndrome (PWS) and to examine the modulating effect on bone of treatment with growth hormone (GH) and sex steroids. This was a cross-sectional study performed in 41 (17 males, 24 females) obese subjects with genetically confirmed PWS, aged 29.4 ± 8.6 years. Forty-six healthy subjects (22 males and 24 females) served as controls. Digitalized X-rays were evaluated at the level of the 2nd metacarpal bone to assess bone geometry, i.e. cross-sectional area (CSA), cortical area (CA), medullary area (MA), metacarpal index (MI) and bone strength evaluated as bending breaking resistance index (BBRI). DEXA was also used to evaluate body composition and bone mineral density (total body, lumbar spine and femoral neck). PWS subjects, after adjusting for height and bone size, had a reduced CSA, CA and BBRI, while bone density was not different. GH treatment had a positive effect and sex steroids a negative effect on bone size and strength. PWS subjects showed a reduced bone size at the metacarpus leading to a reduced strength, while bone density was appropriate for size. GH treatment improves bone geometry but not bone density. Bone strength was significantly reduced in PWS patients who did not receive GH and had been treated with sex steroids.

Assessment of fat-free mass from bioelectrical impedance analysis in obese women with Prader-Willi syndrome.

BACKGROUND: Fat-free mass (FFM) is lower in obese subjects with Prader-Willi syndrome (PWS) than in obese subjects without PWS. FFM prediction equations developed in non-PWS subjects may, thus, not work in PWS subjects. AIM: To test whether the estimation of FFM from bioelectrical impedance analysis (BIA) in PWS subjects requires population-specific equations. METHODS: Using dual-energy X-ray absorptiometry, this study measured FFM in 27 PWS and 56 non-PWS obese women and evaluated its association with the impedance index at 50 kHz (ZI50), i.e. the ratio between squared height and whole-body impedance at 50 kHz. RESULTS: At the same level of ZI50, PWS women had a lower FFM than non-PWS women. However, when PWS-specific equations were used, FFM was accurately estimated at the population level. An equation employing a dummy variable coding for PWS status was able to explain 85% of the variance of FFM with a root mean squared error of 3.3 kg in the pooled sample (n = 83). CONCLUSION: Population-specific equations are needed to estimate FFM from BIA in obese PWS women.

Cyclogram-based evaluation of inter-limb gait symmetry in Prader-Willi Syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is characterized by a complex clinical condition, whose typical features lead to impaired motor and functional skills. To date, limited data is available as regards symmetry of gait in PWS. RESEARCH QUESTION: The aim of this study was to characterize lower-limb asymmetry during gait in a group of Prader-Willi Syndrome (PWS) individuals by using the synchronized cyclograms and to compare it with those of two different control groups, a normal-weight group and an obese group. METHODS: A total of 18 PWS, 30 normal weight (NW) and 28 obese individuals (OG) matched for age, sex and height were assessed via 3D gait analysis. Gait spatio-temporal parameters were computed together with angle-angle diagrams, characterized in terms of their geometric features (i.e. area, orientation, and trend symmetry index). RESULTS: Individuals with PWS exhibit reduced speed, stride length and cadence and increased duration of both stance and double support phase than the other groups. OG was characterized by the same pattern when compared to NW. With respect to inter-limb symmetry, individuals with PWS exhibited significantly larger cyclogram areas at hip joint with respect to the other two groups (203.32 degrees2 vs. 130.73 degrees2 vs. 111.59 degrees2) and significantly higher orientation angle (4.17° vs. 2.11° vs. 1.22°) and Trend Symmetry (3.72 vs. 2.02 vs. 1.21) with respect to the other two groups at knee joint; no differences were found at ankle joint. Both individuals with PWS and those of OG exhibited reduced ROM at knee and ankle joints with respect with normal weight, but no statistically significant differences were observed between PWS and OG. SIGNIFICANCE: The obtained results may provide novel and useful insights to understand better the impairments in motor control associated with this pathological state, supporting clinics in the identification of the best rehabilitation program for this rare pathological state, aimed to improve stability and motor control.

Metabolomic profiling of Prader-Willi syndrome compared with essential obesity.

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/m2), 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/m2). 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.

Corrigendum: Kidney disease in adults with Prader-Willi syndrome: international cohort study and systematic literature review.

[This corrects the article DOI: 10.3389/fendo.2023.1168648.].

Endocrine features of Prader-Willi syndrome: a narrative review focusing on genotype-phenotype correlation.

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment.

Deconvolution-based assessment of pituitary GH secretion stimulated with GHRH+arginine in Prader-Willi adults and obese controls.

OBJECTIVE: The assessment of GH deficiency in adult patients with Prader-Willi syndrome (PWS) has been previously assessed through the evaluation of quantitative parameters, such as the peak value of GH response to exogenous stimuli. A comprehensive description of the pattern of secretory response obtainable by deconvolution analysis is still lacking. The aim of our study was to characterize the time evolution of responses of PWS subjects compared with obese controls. DESIGN AND SUBJECTS: GH responsiveness was measured following the combined administration of GHRH+arginine to 65 PWS adults (24 males, 41 females) aged 18-41·2 years, and 17 age-, gender- and body mass index-matched obese controls. PWS subjects were analysed considering the stratification on different genotypes. MEASUREMENTS: GH response to GHRH+arginine was analysed in terms of peak values, standard area under the curves (AUCs), AUCs due to the stimulus, AUCs of the Instantaneous Secretion Rate signal and Secretion Response Analysis. RESULTS: In terms of both peak values and AUC, GH responses were statistically different between PWS UPD15 and PWS DEL15 subjects as well as between PWS UPD15 and obese controls. PWS subjects showed a lower and a more delayed GH response compared with obese controls. Moreover, PWS UPD15 subjects had the most delayed GH response. CONCLUSIONS: Our findings demonstrate that impaired GH secretion in PWS subjects compared with obese controls regards not only amplitude parameters such as peak value and AUC, but also the shape of the secretory response, which is more delayed, especially for UPD15 subjects.

Central adrenal insufficiency in young adults with Prader-Willi syndrome.

OBJECTIVE: A high prevalence (60%) of central adrenal insufficiency (CAI) has been reported in Prader-Willi syndrome (PWS) using the metyrapone test. We have assessed CAI in adults with PWS using the low-dose short synacthen test (LDSST). DESIGN: Basal cortisol and ACTH, and 30-min cortisol after the administration of 1 µg synacthen, were determined in 53 PWS adults (33 females). A peak cortisol value of ≥500 nmol/l was taken as normal. Hormonal profiles were analysed in relation to gender, genotype and phenotype. Deficient patients were retested by high-dose short synachten test (HDSST) or a repeat LDSST. RESULTS: Mean ± SD basal cortisol and ACTH were 336·6 ± 140·7 nmol/l and 4·4 ± 3·7 pmol/l respectively. Cortisol rose to 615·4 ± 135·0 nmol/l after LDSST. Eight (15·1%) patients had a peak cortisol response <500 nmol/l, with a lower mean ± SD (range) basal cortisol of 184·9 ± 32·0 (138·0-231·7) compared with 364·1 ± 136·6 (149·0-744·5) in normal responders (P < 0·001). Seven of the eight patients underwent retesting, with 4 (7·5%) showing persistent suboptimal responses. Basal and peak cortisol correlated in females (r = 0·781, P < 0·001). Logistic regression revealed that only female gender and baseline cortisol were predictors of cortisol peaks (adjusted R square 0·505). CONCLUSIONS: Although CAI can be part of the adult PWS phenotype, it has a lower prevalence (7·5%) than previously reported. Clinicians are advised to test PWS patient for CAI. Our study also shows that basal cortisol is closely correlated with adrenal response to stimulation, indicating that its measurement may be helpful in selecting patients for LDSST.

Exploring patterns of unwanted behaviours in adults with Prader-Willi syndrome.

BACKGROUND: Obsessive-compulsive (O-C) traits, and excessive food intake are well known behavioural manifestations among individuals with Prader-Willi Syndrome (PWS). Other unwanted behaviours are also frequently observed, but they need a more specific investigation, especially in the adult population. METHODS: The behaviour of 31 PWS adults was investigated via the Symptom Checklist-90-Revised (SCL-90-R), the Yale-Brown Obsessive Compulsive Scale Symptom Checklist (Y-BOCS-SC), and the Prader-Willi Behavioural Checklist (PBC). The PBC is a quick screening questionnaire prompted specifically for the investigation on adults with PWS. RESULTS: Statistical clustering revealed two patterns of unwanted behaviours from the PBC. Behaviours belonging to the first cluster (e.g., Excessive food intake, Skin picking) appear to be linked to the usual phenotypic manifestation of PWS. By contrast, many other behaviours (e.g., some O-C symptoms and aggressive actions) could show a relationship also to individual psychopathologies. CONCLUSIONS: Both internal (Anxiety and Depression) and external (Hostility) difficulties in managing impulses should account for individually distinct behaviours in adults with PWS.

Long-term effects of GH therapy in adult patients with Prader-Willi syndrome: a longitudinal study.

Introduction: Prader-Willi syndrome (PWS) is a complex disorder resulting from the failure of expression of paternal alleles in the PWS region of chromosome 15. The PWS phenotype resembles that observed in the classic non-PWS GH deficiency (GHD), including short stature, excessive fat mass, and reduced muscle mass. To date, a small number of studies on the long-term effects of GH treatment are available in adult subjects with PWS. Methods: In this longitudinal study, 12 obese subjects with PWS (GHD/non-GHD 6/6) were treated for a median of 17 years, with a median GH dose of 0.35 mg/day. The median age was 27.1 years. Anthropometric, body composition, hormonal, biochemical, and blood pressure variables were analyzed in all subjects. Results: Waist circumference was significantly lower at the end of the treatment period (p-value=0.0449), while body mass index (BMI) did not differ significantly. Compared to the baseline, a highly significant reduction of Fat Mass % (FM%) was observed (p-value=0.0005). IGF-I SDS values significantly increased during GH therapy (p-value=0.0005). A slight impairment of glucose homeostasis was observed after GH therapy, with an increase in the median fasting glucose levels, while insulin, HOMA-IR, and HbA1c values remained unchanged. Considering GH secretory status, both subjects with and without GHD showed a significant increase in IGF-I SDS and a reduction of FM% after GH therapy (p-value= 0.0313 for all). Discussion: Our results indicate that long-term GH treatment has beneficial effects on body composition and body fat distribution in adults with PWS associated with obesity. However, the increase in glucose values during GH therapy should be considered, and continuous surveillance of glucose metabolism is mandatory during long-term GH therapy, especially in subjects with obesity.

Differences in spinal postures and mobility among adults with Prader-Willi syndrome, essential obesity, and normal-weight individuals.

Introduction: Spinal kinematics/motion are reported to be altered in adolescents and adults with essential obesity, while no information is available in patients with Prader-Willi syndrome so far. The aim of this study was to examine cross-sectionally the characteristics of spinal postures and mobility in 34 patients with PWS, in 35 age- and sex-matched adults with essential obesity, and in 37 normal-weight individuals. Methods: Spinal posture and mobility were assessed using a radiation-free back scan, the Idiag M360 (Idiag, Fehraltorf, Switzerland). Differences in spinal posture and mobility between the three groups were determined using a two-way analysis of variance. Results: Adults with Prader-Willi syndrome had greater thoracic kyphosis [difference between groups (Δ) = 9.60, 95% CI 3.30 to 15.60, p = 0.001], less lumbar lordosis (Δ = -6.50, 95% CI -12.70 to -0.30, p = 0.03) as well as smaller lumbar and hip mobility than those with normal weight. Discussion: Although the characteristics of the spine in patients with Prader-Will syndrome appear to be similar to that found in subjects with essential obesity, Prader-Willi syndrome was found to influence lumbar movements more than thoracic mobility. These results provide relevant information about the characteristics of the spine in adults with Prader-Willi syndrome to be taken into careful consideration in the management of spinal conditions. These findings also highlight the importance of considering the musculoskeletal assessment of spinal postures and approaches targeting spinal and hip flexibility in adults with Prader-Willi syndrome.

Proteome profiling identifies circulating biomarkers associated with hepatic steatosis in subjects with Prader-Willi syndrome.

Introduction: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by loss of expression of paternal chromosome 15q11.2-q13 genes. Individuals with PWS exhibit unique physical, endocrine, and metabolic traits associated with severe obesity. Identifying liver steatosis in PWS is challenging, despite its lower prevalence compared to non-syndromic obesity. Reliable biomarkers are crucial for the early detection and management of this condition associated with the complex metabolic profile and cardiovascular risks in PWS. Methods: Circulating proteome profiling was conducted in 29 individuals with PWS (15 with steatosis, 14 without) using the Olink Target 96 metabolism and cardiometabolic panels. Correlation analysis was performed to identify the association between protein biomarkes and clinical variables, while the gene enrichment analysis was conducted to identify pathways linked to deregulated proteins. Receiver operating characteristic (ROC) curves assessed the discriminatory power of circulating protein while a logistic regression model evaluated the potential of a combination of protein biomarkers. Results: CDH2, CTSO, QDPR, CANT1, ALDH1A1, TYMP, ADGRE, KYAT1, MCFD, SEMA3F, THOP1, TXND5, SSC4D, FBP1, and CES1 exhibited a significant differential expression in liver steatosis, with a progressive increase from grade 1 to grade 3. FBP1, CES1, and QDPR showed predominant liver expression. The logistic regression model, -34.19 + 0.85 * QDPR*QDPR + 0.75 * CANT1*TYMP - 0.46 * THOP1*ALDH1A, achieved an AUC of 0.93 (95% CI: 0.63-0.99), with a sensitivity of 93% and specificity of 80% for detecting steatosis in individuals with PWS. These biomarkers showed strong correlations among themselves and were involved in an interconnected network of 62 nodes, related to seven metabolic pathways. They were also significantly associated with cholesterol, LDL, triglycerides, transaminases, HbA1c, FLI, APRI, and HOMA, and showed a negative correlation with HDL levels. Conclusion: The biomarkers identified in this study offer the potential for improved patient stratification and personalized therapeutic protocols.