Prader-Willi Research Articles

Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor

BackgroundPrader-Willi syndrome (PWS) is a rare genetic neurodevelopmental syndrome with highly increased risk of obesity and cardiovascular disease (CVD). Recent evidence suggests that inflammation is implicated in the pathogenesis. Here we investigated CVD related immune markers to shed light on pathogenetic mechanisms.MethodsWe performed a cross-sectional study with 22 participants with PWS and 22 healthy controls (HC), and compared levels of 21 inflammatory markers that reflect activity in different aspects of CVD related immune pathways and analyzed their association with clinical CVD risk factors.ResultsSerum levels of matrix metalloproteinase 9 (MMP-9) was (median (range)) 121 (182) ng/ml in PWS versus 44 (51) ng/ml in HC, p = 1 × 10-9), myeloperoxidase (MPO) was 183 (696) ng/ml versus 65 (180) ng/ml, p = 1 × 10-5) and macrophage inhibitory factor (MIF) was 46 (150) ng/ml versus 121 (163) ng/ml (p = 1 × 10-3), after adjusting for age and sex. Also other markers tended to be elevated (OPG, sIL2RA, CHI3L1, VEGF) but not significantly after Bonferroni correction (p > 0.002). As expected PWS had higher body mass index, waist circumference, leptin, C-reactive protein, glycosylated hemoglobin (HbA1c), VAI and cholesterol, but MMP-9, MPO and MIF remained significantly different in PWS after adjustment for these clinical CVD risk factors.ConclusionPWS had elevated levels of MMP-9 and MPO and of reduced levels of MIF, which were not secondary to comorbid CVD risk factors. This immune profile suggests enhanced monocyte/neutrophil activation, impaired macrophage inhibition with enhanced extracellular matrix remodeling. These findings warrant further studies targeting these immune pathways in PWS.

Examining Effective Intervention Strategies in a Play-Based Program for Children with Prader-Willi Syndrome

Examining Effective Intervention Strategies in a Play-Based Program for Children with Prader-Willi Syndrome

The importance of gynecological examination in adolescent girls and adult women with Prader-Willi syndrome.

Current published guidelines for routine care of women with Prader-Willi syndrome (PWS) do not include recommendations for gynecologic examinations. We describe our experience with gynecological examinations in women with PWS and offer recommendations for routine health care for these patients. Data were collected on all 41 PWS females ages ≥12 year, followed in our national Israeli multidisciplinary clinic between the years 2011 and 2022. Menstrual data and findings on external gynecological examination, including evaluation of the vulva and hymen were recorded at yearly visits. During the gynecological evaluation the topic of sexual education was discussed. Pelvic ultrasound, specifically for antral follicular count, was performed for those visiting the clinic during 2020-2022. Blood samples for luteinizing hormone (LH), follicular stimulating hormone (FSH), and estradiol were obtained routinely and DEXA scans for bone density were done when indicated. Of the 41 women, (median age at start of follow-up 17 years, range [12.3-39], BMI 30.4 kg/m2 [IQR 23.5-37.1]), 39 women agreed to external gynecological examination. Eleven women (27%) had spontaneous menses, with menarche at the age of 14 to as late as 31 years. The hymen was intact in all except one. Poor hygiene was observed in eight women, three women with vulvovaginitis, and five with irritated vulva related to poor hygiene. Gynecological ultrasound was performed in 27 women. In 22, endometrial thickness was less than 5 mm. The median antral follicular count (AFC) was 6 (<10th percentile for age). No correlation between AFC and menstruation or BMI was found. Mean FSH level was 5.7 ± 3.6 IU, LH was 2.29 ± 2.23, and estradiol was 128 ± 76 pmol/L. Data on DEXA measurements were available in 25 women aged 16-39. Median spine T score was -1.3 (range between 0.5 and -3.7), and hip T score was -1.2 (range between 0.8 and -3.3). A negative correlation was found between endometrial thickness and the presence of osteopenia or osteoporosis (r = -0.5, p = 0.013). Despite our recommendations, only eight of 14 women agreed to hormonal treatment or contraception. One woman who received treatment had a thromboembolic event. Routine health care for women with PWS should include gynecological examinations. The gynecological evaluation should include external genital examination, assessment of hygiene, obtaining a blood sample for hormone levels, and documenting a history of sexual experience or sexual abuse. Hormonal treatment or contraception should be offered when appropriate.

Neurodevelopmental Manifestations and Birth Defects in Prader-Willi Syndrome: Findings from a Study in Western Ukraine

Prader-Willi syndrome (PWS) is a genetic disease characterized by mental retardation, as well as autism spectrum disorders, obesity and mood disorders. The aim of our study was to research a spectrum of genetic heterogenity and different clinical neurodevelopmental manifestations. Materials and methods: clinical, molecular, genetic and psychological methods were used. We observed 9 children (5 boys and 4 girls) with Prader-Willi syndrome from Lviv and Ivano-Frankivsk regions (Western Ukraine) who were diagnosed and followed-up at the Institute of Hereditary Pathology, National Academy of Medical Sciences of Ukraine, Lviv, for 4 years (2019–2022) and underwent molecular genetic testing. The ages of children ranged from 1 month to 7 years, with the mean value amounting to 3.6 years of age. Results: Our study revealed that 6 (66.7%) out of 9 children with PWS had birth defects. At ultrasound during pregnancy, we observed certain clinical features of the fetus, including fetal intrauterine development delay –5 (55.5%), and higher nuchal translucency measurement – 3 (33.3%). According to the checklist of autism spectrum disorders (CASD), 3 of the examined children with autism syndrome were at risk and required further monitoring, while 5 children scored 18-20 points, which indicated the presence of autistic spectrum and required in-depth monitoring during diagnosis. Stereotypical and repetitive play as a manifestation of problems with social interaction was observed in 3 boys with PWS. In our study, parents had no complaints about aggressive behavior in children with this syndrome. Conclusions: In cases if the children have signs of autism or developmental delay, they should undergo genetic counseling.

Recuperação nutricional pós-operatória em paciente oncológico em idade adulta: revisão de literatura

Sabe-se que o preparo do paciente cirúrgico em seu contexto nutricional traz resultados claros quanto à evolução pós-operatória. Tal conhecimento, já embasado na literatura, ganha ainda mais destaque quando é feito um recorte populacional sob a ótica dos pacientes oncológicos, assim, a boa condução nutricional pós-operatório se faz necessária. Para a realização deste trabalho, optou-se por uma revisão sistemática integrativa baseada em seis etapas. Optou-se pela utilização do método PICOT, sendo formulado a pergunta a ser respondida nesta revisão: “É possível realizar medidas clínicas e nutricionais no pós-operatório para auxiliar o paciente adulto oncológico na recuperação do procedimento cirúrgico, diminuindo o número de complicações e tempo de internação?" Para o recorte temporal deste trabalho, foram utilizados artigos publicados entre os anos de 2013 e 2023. Além disso, para a escolha dos artigos, foram selecionados textos em inglês e português. Após pré seleção e seleção a partir da aplicação dos critérios de inclusão e exclusão foram identificados vinte e nove (29) artigos, dos quais dois (2) são revisões sistemáticas, quatro (4) estudos observacionais, um (1) estudos qualitativos prospectivos, quinze (15) ensaios clínicos controlados e sete (7) meta análises. A literatura sustenta que a recuperação precoce da dieta oral, mesmo em baixas taxas iniciais (suficiência energética diária &gt;25%), melhora o estado nutricional, bem como reduz a mortalidade. Outra alternativa apresentada pelos estudos para a definição das vias alimentares é a definição da inserção da sonda enteral. Embora não seja preferível, pois sempre se deve buscar a via alimentar mais próxima da fisiológica, muitas vezes a nutrição parenteral é necessária. A suplementação nutricional pós-operatória, tanto parenteral quanto enteral, com ácidos graxos poliinsaturados (PUFA), como o ômega-3, associados a aminoácidos, como glutamina e arginina, demonstrou relevância estatística na redução de complicações infecciosas secundárias no pós-operatório. Os estudos ainda divergem sobre a redução da mortalidade em comparação com a nutrição enteral padrão. Estudos mais robustos podem ser necessários para descartar ou impor tal prática de suplementação nutricional. Ainda há uma tentativa de suplementação de proteína total em dietas orais e enterais na tentativa de melhorar a recuperação pós-operatória. A associação de uma dieta rica em proteínas no pós-operatório imediato com o uso concomitante de fibras dietéticas (Fibra Alimentar Frutooligossacarídeo) também foi estudada. O número de pacientes com diagnóstico tardio em estágios oncológicos avançados ainda é uma realidade preocupante, principalmente após o advento da COVID-19. Os cuidados pós-operatórios para reabilitação nutricional carecem de estudos mais robustos para indica com maior segurança um protocolo geral de manejo. terapias de imunomodulação podem apresentar boa resposta quando utilizadas no período pós-operatório.

O-199 Imprinting disorders in singletons conceived by assisted reproductive technology in Sweden

Abstract Study question Is singleton birth from assisted reproductive technology (ART) associated with imprinting disorders (IDs) independent of parental infertility and other background factors? Summary answer Singletons conceived using intracytoplasmic sperm injection (ICSI) and frozen embryos have higher risks of Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS) and Silver-Russell syndrome (SRS). What is known already Previous studies have suggested elevated risk of IDs in children conceived with ART compared with children conceived with spontaneous conception (SC). It is not clear to what extent the observed associations could be explained by parental infertility and related risk factors. Knowledge on specific ART procedures and their association with IDs is also limited. Study design, size, duration A nationwide register-based cohort study was carried out in which all liveborn singletons in 1997-2017 in Sweden were included with follow-up to 2018. Participants/materials, setting, methods Among 1 998 825 singletons, 60 210 were conceived using ART. The International Classification of Diseases (ICD) version 10 was used to identify three distinct ID groups: PWS/SRS, BWS, and central precocious puberty (CPP). Cox regression, combined with inverse probability treatment weights to account for birth year, parity, pregnancy loss history, parental age and country of origin, was used to compare ART singletons with all SC singletons and those born to couples with known infertility. Main results and the role of chance A total of 1012 children were diagnosed with the IDs of interest (654 PWS/SRS, 255 BWS, and 109 CPP), and 49 of them were conceived through ART. Compared with all SC singletons, higher risk of PWS/SRS and BWS was observed in ART singletons and the weighted hazard ratios (wHRs) were 1.57 [95% CI, 1.09-2.26] and 2.57 [95% CI, 1.60-4.12], respectively. The elevated risks remained when comparison was restricted to SC singletons of couples with known infertility, though the wHR for BWS was somewhat attenuated (1.87, 95% CI: 1.04-3.36). No difference in risk of CPP was observed between singletons conceived with and without ART irrespective of parental infertility. Further subgroup analysis revealed that ICSI in combination with frozen embryo transfer was responsible for the higher risks of PWS/SRS (wHR 6.32, 95% CI: 3.34-11.95) and BWS (wHR 9.04, 95% CI: 4.34-18.82). Limitations, reasons for caution The use of the Swedish ICD-10 did not allow distinction of PWS and SRS. The number of CPP cases in ART singletons was too small (N = 3) to make inference. Wider implications of the findings This study found that ART-conceived singletons, particularly those conceived using ICSI and frozen embryos, had a higher risk of IDs independent of parental infertility. However, the underlying mechanism is not clear, and the role of type and severity of infertility warrants further investigation. Trial registration number not applicable

Schaaf-Yang Syndrome: Clinical Phenotype and Effects of 4 years of Growth Hormone Treatment

Introduction: Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder caused by truncating mutations of the MAGEL2 gene, located in the Prader-Willi syndrome (PWS) region. PWS and SYS have phenotypic overlap. Patients with SYS are often treated with growth hormone (GH), but evidence for the effectiveness of the treatment in patients with SYS is limited. Methods: This study describes 7 children with SYS. We studied their phenotype, genotype, and the effect of GH treatment on height and body mass index (BMI) during 4 years and on body composition during 1 year. Results: All patients had a normal birth weight. Most patients had hypotonia and feeding difficulties after birth (86%). Full-scale IQ ranged from <50 to 92. All patients above the age of 2 years had psycho-behavioral problems. There were no apparent correlations between the phenotype and the location of the defect in the MAGEL2 gene. Mean (95% CI) height SDS increased significantly from −1.74 (−3.55; 0.07) at start to −0.05 (−1.87; 1.77) after 4 years of GH treatment. Mean (95% CI) BMI SDS decreased significantly from 2.01 (1.02; 3.00) to 1.22 (0.18; 2.26) after 6 months and remained the same during the rest of the follow-up. Fat mass percentage SDS decreased and lean body mass did not change during 1 year of treatment in 3 patients. Conclusion: Patients presented with a phenotype of hypotonia, respiratory insufficiency, and feeding difficulties after birth, endocrine disorders, intellectual disability, and behavioral problems. Treatment with GH significantly improved height SDS and BMI over the course of 4 years.

Generation of an induced pluripotent stem cell line, ZIPi021-A, from fibroblasts of a Prader-Willi syndrome patient with maternal uniparental disomy (mUPD)

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by loss of paternal expression of imprinted genes on chromosome 15q11-q13. We established a human induced pluripotent stem cell line (hiPSC), ZIPi021-A, from fibroblasts of a 4-year-old female PWS patient with the subtype of maternal uniparental disomy (mUPD). The generated hiPSC line was transgene-free, expressed pluripotency markers and showed the ability to differentiate into all three germ layers in vitro. The ZIPi021-A hiPSC line could be used as a cellular model for PWS in humans.

A Personalized Approach to Determining the Caloric Needs of Children with Prader-Willi Syndrome Treated with Growth Hormone.

Prader-Willi Syndrome (PWS) is the most frequent cause of genetic obesity. Early reports indicate that children with PWS require 20-40% fewer calories than healthy children to maintain adequate growth. Growth hormone treatment for children with PWS, approved in 2000, affects the body composition and probably affects energy requirements. This retrospective cross-sectional study analyzed the caloric intake in children with PWS aged from 6 months to 12 years old who underwent growth hormone treatment, comparing the patients' caloric intake calculated from parent-recorded dietary intake versus the recommended caloric intake for healthy children, taking into account the age, sex, height, weight, and physical activity. We analyzed the data from 25 patients (13 (52%) boys; mean age, 6.72 ± 2.81 y; median age at starting growth hormone treatment, 1.4 y (IQR: 0.78-2.29); 17 (68%) normal weight and 8 (32%) overweight or obese). The mean daily energy intake was 1208 ± 186 kcal/d, representing 96.83% ± 18.66 of the recommended caloric intake for healthy children. The caloric intake in children with PWS treated with growth hormone was very similar to that recommended for healthy children; thus, we should rethink the dietary recommendations for these children.

Oxytocin's Regulation of Thermogenesis May Be the Link to Prader-Willi Syndrome.

Prader-Willi Syndrome (PWS) is a genetic neurodevelopmental disorder that is caused by either the deletion of the paternal allele of 15q11-q13, maternal uniparental disomy of chromosome 15 or defects in the chromosome 15 imprinting centre and is characterized by cognitive impairment, hyperphagia and low metabolic rate with significant risk of obesity, as well as a variety of other maladaptive behaviours and autistic spectrum disorder (ASD). Many of the features seen in PWS are thought to be due to hypothalamic dysfunction resulting in hormonal abnormalities and impaired social functioning. The preponderance of evidence indicates that the Oxytocin system is dysregulated in PWS individuals and that this neuropeptide pathways may provide promising targets for therapeutic intervention although the process by which this dysregulation occurs in PWS awaits mechanistic investigation. PWS individuals present abnormalities in thermoregulation an impaired detection for temperature change and altered perception of pain indicating an altered autonomic nervous system. Recent studies indicate that Oxytocin is involved in thermoregulation and pain perception. This review will describe the update on PWS and the recent discoveries on Oxytocin regulation of thermogenesis together with the potential link between Oxytocin regulation of thermogenesis and PWS to create a new groundwork for the treatment of this condition.

Food socialization of children with Prader-Willi syndrome: an interdisciplinary problematization.

Eating "disorders" of people with Prader-Willi syndrome are frequently reported in the biomedical literature. The eating behaviors are presented as a syndrome-specific trajectory over the course of a lifetime. Infants initially show anorexic behavior, which then develops into hyperphagia that lasts from childhood to adulthood and is characterized by strong cravings for food and relentless thinking about it. However, the sociocultural determinants of these food practices are not fully understood. In the first section of this article, we carry out a literature review of medical articles published on disordered eating in children with PWS. The second section draws on a social science perspective and offers an interdisciplinary problematization using the concept of food socialization. To conclude, the third section explores the challenges facing research and new questions that emerge from the alternative problematization that is the PWS Food Social Norms Internalization (FSNI) theory.

Early onset critically ill infants with Schaaf-Yang syndrome: a retrospective study from the China neonatal genomes project and literature review.

Schaaf-Yang syndrome (SYS) is a recently identified rare neurodevelopmental disorder characterized by neonatal hypotonia, feeding difficulty, joint contractures, autism spectrum disorder and development delay/intellectual disability. It is mainly caused by truncating variants in maternally imprinted gene MAGEL2 within the Prader-Willi syndrome critical region 15q11-q13. Clinical diagnosis of SYS is difficult for clinicians due to its rarity and highly variable phenotypes, while unique inheritance patterns also complicate genetic diagnosis. To date, no published papers have analyzed the clinical consequences and molecular changes in Chinese patients. In this study, we retrospectively investigated the mutation spectrums and phenotypic features of 12 SYS infants. The data were from a cohort of critically ill infants from the China neonatal genomes project (CNGP), sponsored by Children's Hospital of Fudan University. We also reviewed relevant literature. Six previously reported mutations and six novel pathogenic variations of MAGEL2 were identified in 12 unrelated infants. Neonatal respiratory problems were the major complaint for hospitalization, which occurred in 91.7% (11/12) cases. All babies displayed feeding difficulties and a poor suck postnatally, and neonatal dystonia was present in 11 of the cases; joint contractures and multiple congenital defects were also observed. Interestingly, we found that 42.5% (57/134) of the reported SYS patients, including ours carried variants in the c.1996 site, particularly the c.1996dupC variant. The mortality rate was 17.2% (23/134), with the median age of death between 24 gestational weeks in fetuses and 1-month-old in infants. Respiratory failure was the leading cause of death in live-born patients (58.8%, 10/17), especially during the neonatal period. Our findings expanded the genotype and phenotype spectrum of neonatal SYS patients. The results demonstrated that respiratory dysfunction was a typical characteristic among Chinese SYS neonates that should attract physicians' attention. The early identification of such disorders allows early intervention and can further provide genetic counseling as well as reproductive options for the affected families.

Prader -Willi Syndrome: Deletion of Chromosome 15q11.2-q13 in Paternal Allele

Prader Willi Syndrome (PWS) is one of the most common genetic condition of childhood morbid obesity. Absence of expression of the paternally active genes on the long arm of chromosome 15 is responsible for this syndrome. A 4-year-old girl, presented with excessive weight gain since early infancy. She has developmental delay, mental retardation and Her physical features were suggestive of Prader-Willi syndrome. MS PCR detected deletion of the specific chromosomal region 15q11.2-q13 in the paternal allele which is causative of Prader-Willi syndrome. The syndrome has no cure but multidisciplinary approaches are available to improve associated problems. We confirm the case of Prader Willi Syndrome by genetic analysis, which is important for those who present with obesity and mental retardation. Bangladesh Medical Res Counc Bull 2022; 48(3): 244-248

The relationship between endogenous oxytocin and vasopressin levels and the Prader-Willi syndrome behaviour phenotype.

Oxytocin and vasopressin systems are altered in Prader Willi syndrome (PWS). However, investigations into endogenous oxytocin and vasopressin levels as well as clinical trials evaluating the effect of exogenous oxytocin on PWS symptoms have had mixed results. It is also unknown whether endogenous oxytocin and vasopressin levels are associated with certain PWS behaviours. We compared plasma oxytocin and vasopressin and saliva oxytocin levels in 30 adolescents and adults with PWS to 30 typically developing age-matched controls. We also compared neuropeptide levels between gender and genetic subtypes within the PWS cohort and examined the relationship between neuropeptide levels and PWS behaviours. While we did not measure a group difference in plasma or saliva oxytocin levels, plasma vasopressin was significantly lower in individuals with PWS compared to controls. Within the PWS cohort, saliva oxytocin levels were higher in females compared to males and individuals with the mUPD compared to the deletion genetic subtype. We also found the neuropeptides correlated with different PWS behaviours for males and females and for genetic subtypes. For the deletion group, higher plasma and saliva oxytocin levels were related to fewer behaviour problems. For the mUPD group, higher plasma vasopressin levels were related to more behaviour problems. These findings support existing evidence of a vasopressin system defect in PWS and for the first time identify potential differences in the oxytocin and vasopressin systems across PWS genetic subtypes.

Behavioral services for individuals with Prader–Willi Syndrome: An initial examination of experiences, needs, and wants of caregivers

AbstractPrader–Willi Syndrome (PWS) is a rare neurogenetic disorder that presents with a variety of behaviors that could be considered challenging by caregivers, including excessive food consumption and volatile tantrums. Although these behavior challenges can be dangerous and interfere with successful daily living, previous research suggests that caregivers have trouble accessing effective interventions. Twenty‐seven caregivers of individuals with PWS completed a survey to assess their needs and wants for services addressing behavioral challenges related to PWS. The survey was classified into four sections: prevalence of behavioral concerns, current access or barriers to accessing behavioral supports, familiarity with applied behavior analysis (ABA), and specific needs when accessing behavioral services. Data were analyzed using descriptive statistics. Although caregivers reported struggling with behaviors, such as tantrums, repetitive behaviors, and rigidity, many identified barriers to accessing treatment, including difficulty in finding services or practitioners familiar with PWS. Applied behavior analysis shows potential for addressing many of the behavioral challenges associated with PWS reported by caregivers. As caregivers of PWS continue to advocate for ABA‐based therapy for the individuals they support, practitioners need to take into account the needs and wants of PWS caregivers and specific behavioral needs of individuals with PWS.

Pediatric Sleep Respiratory Disorders: A Narrative Review of Epidemiology and Risk Factors

Sleep is a fundamental biological necessity, the lack of which has severe repercussions on the mental and physical well-being in individuals of all ages. The phrase “sleep-disordered breathing (SDB)” indicates a wide array of conditions characterized by snoring and/or respiratory distress due to increased upper airway resistance and pharyngeal collapsibility; these range from primary snoring to obstructive sleep apnea (OSA) and occur in all age groups. In the general pediatric population, the prevalence of OSA varies between 2% and 5%, but in some particular clinical conditions, it can be much higher. While adenotonsillar hypertrophy (“classic phenotype”) is the main cause of OSA in preschool age (3–5 years), obesity (“adult phenotype”) is the most common cause in adolescence. There is also a “congenital–structural” phenotype that is characterized by a high prevalence of OSA, appearing from the earliest ages of life, supported by morpho-structural abnormalities or craniofacial changes and associated with genetic syndromes such as Pierre Robin syndrome, Prader-Willi, achondroplasia, and Down syndrome. Neuromuscular disorders and lysosomal storage disorders are also frequently accompanied by a high prevalence of OSA in all life ages. Early recognition and proper treatment are crucial to avoid major neuro-cognitive, cardiovascular, and metabolic morbidities.

Distinct Lipids Profiles and Associations With Clinical Indicators and Gut Microbiota in Children With Prader-Willi Syndrome.

Lipid metabolism is closely linked to adiposity. Prader-Willi syndrome (PWS) is a typical genetic disorder causing obesity; however, the distinct lipidomic profiles in PWS children have not been thoroughly investigated. Herein, serum lipidomics analyses were simultaneously explored in PWS, simple obesity (SO), and normal children (Normal). Results indicated that the total concentration of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in the PWS group were significantly deceased compared with both the SO and the Normal group. In contrast, compared with the Normal group, there was an overall significant increase in triacylglycerol (TAG) levels in both the PWS and the SO groups, with the highest found in SO group. Thirty-nine and 50 differential lipid species were screened among 3 groups: between obesity (PWS and SO) and the Normal group. Correlation analysis revealed distinct profiles in PWS that was different from other 2 groups. Notably, PC (P16:0/18:1), PE (P18:0-20:3), PE (P18:0-20:4)) showed significant negative correlation with body mass index (BMI) only in the PWS group. PE (P16:0-18:2) showed a negative association with BMI and weight in the PWS group, but significant positive correlation in the SO group; no statistically significant association was found in the Normal group. We also found a significant negative correlation between Blautia genus abundance and several significantly changed lipids, including LPC (14:0), LPC (16:0), TAG (C50:2/C51:9), TAG (C52:2/C53:9), TAG (C52:3/C53:10), and TAG (C52:4/C53:11), but no significant correlation in the Normal group and the SO group. Similarly, in the PWS group, the Neisseria genus was significantly negatively associated with acylcarnitine (CAR) (14:1), CAR (18:0), PE (P18:0/20:3), and PE (P18:0/20:4), and extremely positively associated with TAG (C52:2/C53:9); no obvious correlations were observed in the Normal group and the SO group.

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

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. 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. 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). 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.

Prader-Willi syndrome: innovative rehabilitation technologies

The article discusses the rare and difficult to diagnose and treat Prader–Willi syndrome (PWS). The review part of the article presents the issues of its epidemiology, genetic and clinical manifestations of PWS; the role of hypothalamic dysfunction leading to growth hormone defi ciency, hypogonadism, hypothyroidism, adrenal insufficiency, risk of obesity, metabolic syndrome is emphasized. The results of studies concerning speech and intellectual development delay and neuropsychiatric disorders in children with PWS are presented. On the example of clinical observation of a child with this genetic syndrome, along with known methods of treatment, modern possibilities of using innovative rehabilitation technologies, including transcranial micropolarization and bioacoustic correction, are shown.

Acute stress response of the HPA-axis in children with Prader-Willi syndrome: new insights and consequences for clinical practice.

Prader-Willi syndrome (PWS) is associated with hypothalamic dysfunction. It has been reported that the HPA axis might show a delayed response during acute stress, and it is unknown whether the response of the HPA-axis during acute stress changes with age in children with PWS. To investigate the HPA-axis response during an overnight single-dose metyrapone (MTP) test in children with PWS and to assess if the response changes with age, whether it is delayed and if it changes with repeated testing over time. In addition, we evaluated different cut-off points of ACTH and 11-DOC levels to assess stress-related central adrenal insufficiency (CAI). An overnight single-dose MTP test was performed in 93 children with PWS. Over time, 30 children had a second test and 11 children a third one. Children were divided into age groups (0-2 years, 2-4 years, 4-8 years and > 8 years). Most children did not have their lowest cortisol level at 7.30h, but at 04.00h. Their ACTH and 11-DOC peaks appeared several hours later, suggesting a delayed response. When evaluated according to a subnormal ACTH peak (13-33 pmol/L) more children had an subnormal response compared to evaluation based on a subnormal 11-doc peak (< 200 nmol/L). The percentage of children with a subnormal ACTH response ranged from 22.2 to 70.0% between the age groups, while the percentage of a subnormal 11-DOC response ranged from 7.7 to 20.6%. When using the ACTH peak for diagnosing acute-stress-related CAI, differences between age groups and with repeated testing over time were found, whereas there was no age difference when using the 11-DOC peak. Early morning ACTH or 11-DOC levels are not appropriate to determine acute stress-related CAI in children with PWS, thus multiple measurements throughout the night are needed for an accurate interpretation. Our data suggest a delayed response of the HPA-axis during acute stress. Using the 11-DOC peak for the test interpretation is less age-dependent than the ACTH peak. Repeated testing of the HPA-axis over time is not required, unless clinically indicated.