Effect of non-pharmacological intervention on the nutritional status of patients with Prader Willi Syndrome.

INTRODUCTION: Obesity is highly prevalent in patients with Prader-Willi syndrome (PWS), particularly among adults. This condition, which can be morbid in many cases, is multifactorial and has a complex management. The purpose of our study was to describe the feasibility of achieving a better nutritional status, including normal weight in individuals diagnosed with PWS, through specific nutritional interventions within the framework of a transdisciplinary treatment and without resorting to pharmacological treatments or growth hormone (GH). METHODOLOGY: This observational study included patients with confirmed genetic diagnosis of PWS, receiving transdisciplinary treatment in a specialized rare diseases institution. Patients under treatment with GH and those under pharmacological treatment with nutritional objectives were excluded from the study. All patients attended our institution regularly on a weekly or fortnightly basis. Anthropometric records, including weight, height, and body mass index (BMI) were evaluated in each visit from treatment onset until the last check-up. RESULTS: We included 24 patients with confirmed genetic diagnosis of PWS. At baseline, 9 patients (38 %) had obesity grade III, 1 (4 %) of obesity grade II, 10 (42 %) of obesity grade I, 2 (8 %) of overweight, and 2 patients (8 %) with normal baseline weight. After a median duration of 52 months (interquartile range 23-116 months) of transdisciplinary nutritional treatment, we identified a significant reduction in BMI (baseline 40.2 ± 15.7 kg/m2 vs. follow-up 28.3 ± 6.7 kg/m2, p < 0.0001), without significant differences regarding height (baseline 1.45 ± 0.1 m vs. follow-up 1.48 ± 0.1 m, p = 0.09). CONCLUSION: In this study, we demonstrated that nutritional nonpharmacologic interventions immersed in a transdisciplinary treatment enabled a consistent and sustainable improvement in BMI and nutritional status among patients with PWS.

Effectiveness of a transdisciplinary approach on hyperphagia management among patients with Prader Willi syndrome.

BACKGROUND: One of the main characteristics of Prader Willi syndrome (PWS) is hyperphagia and obesity. This study sought to evaluate behaviours related to hyperphagia in individuals with PWS under a non-pharmacological transdisciplinary approach. METHODS: This observational study included PWS patients under a traditional non-pharmacological nutritional approach immersed within a regular transdisciplinary treatment (RTT) and a control group of PWS individuals without RTT. All individuals were evaluated using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). RESULTS: Forty-three individuals were evaluated. The mean age at baseline (treatment onset) was 18.4±8.3 years in the RTT group and 19.1±6.9 years in the control group (p=0.74). Hyperphagia-related behaviours were significantly lower among those under RTT (RTT 5.7±3.7 vs control 13.1±7.5, p<0.0001). This was also identified within the three categories: arguing or manipulating to obtain food (2.71±2.1 vs 5.41±3.2, p=0.003), sneaking food (1.33±1.5 vs 3.55±3.3, p=0.007), and anger or tantrums related to food (1.67±1.8 vs 4.09±2.7, p=0.001). After a mean treatment duration of 41.0 months, the RTT group had a reduction in body mass index (baseline 38.7±17.1kg/m2 vs follow-up 29.2±9.2kg/m2; p<0.0001). A significant association between RTT duration and BMI reduction (p=0.037) was identified. CONCLUSION: We observed a positive impact on behaviours related to hyperphagia and a BMI reduction in PWS individuals in a context of a non-pharmacological nutritional approach as part of an RTT.

Transcranial Direct Current Stimulation for Prader-Willi Syndrome.

BACKGROUND: Given the limited therapeutic options for Prader-Willi syndrome (PWS), we conducted an open-label clinical trial to evaluate the effects of transcranial direct current stimulation (tDCS) for hyperphagia, food craving, and aberrant behaviors on this population. METHODS: Twelve subjects with PWS (11-35 years old) were included. The subjects underwent 10 daily 20-minute sessions of tDCS in 2 weeks. The anode was positioned over the left dorsolateral prefrontal cortex, and the cathode over the contralateral region. RESULTS: We observed amelioration of hyperphagic and food craving symptoms (P < 0.05), as well as amelioration of behavioral symptoms measured with the Aberrant Behavior Checklist (P < 0.05). DISCUSSION: To our knowledge, this is the first proof-of-concept trial to report the positive effects of increasing excitability of the left dorsolateral prefrontal cortex, using tDCS, for the behavioral, hyperphagia, and food craving symptoms in PWS, which is a low-cost, well-studied, safe alternative for brain stimulation.

Intervención multidisciplinaria en paciente diagnosticado con el síndrome de Prader-Will / Interdisciplinary intervention in a pacient diagnosed with Prader-Willi síndrome

Introducción: El síndrome de Prader-Willi es una enfermedad genética, causada por deleciones de novo en la región 15q11q13 en el cromosoma paterno. Se caracteriza por falta de saciedad que conduce a obesidad mórbida, trastornos del comportamiento, discapacidad intelectual, baja estatura e hipogonadismo. Objetivo: Describir los resultados obtenidos del análisis e intervención multidisciplinar realizados en paciente diagnosticado con el síndrome de Prader-Willi. Presentación del caso: Análisis de caso clínico en menor de 8 años, sexo masculino, diagnosticado con síndrome de Prader-Willi, a través de intervención multidisciplinaria realizado en tres momentos: evaluación, diagnóstico e intervención con enfoque cognitivo conductual. Conclusiones: Las estrategias adoptadas generaron cambios significativos en el contexto familiar y social, entre ellas, apropiación de las recomendaciones suministradas, adopción de factores protectores, identificación de roles y optimización en la adherencia farmacológica. La atención a estas consideraciones proporciona mejoras, que apuntan a la calidad de vida y clínica del paciente(AU)

Introduction: Prader-Willi syndrome is a genetic disease caused by de novo deletions in the 15q11q13 region in the paternal chromosome. It is characterized by lack of satiety leading to morbid obesity, behavioral disorders, intellectual disability, short height and hypogonadism. Objective: To describe the results obtained from the multidisciplinary analysis and intervention performed in a patient diagnosed with Prader-Willi syndrome. Presentation of the clinical case: Clinical case analysis in an 8 years old child, male sex, diagnosed with Prader-Willi syndrome through a multidisciplinary intervention performed in three moments: assessment, diagnosis and intervention with cognitive behavioral approach. Conclusions: The strategies adopted generated significant changes in the social and family context, family´s appropriation of the recommendations provided, adoption of protective factors, roles identification and improving of adherence to treatment. By taking into account this considerations, improvements lead to clinic and life quality of the patient(AU)

PRADER-WILLI SYNDROME: WHAT IS THE GENERAL PEDIATRICIAN SUPPOSED TO DO? - A REVIEW. / SÍNDROME DE PRADER WILLI: O QUE O PEDIATRA GERAL DEVE FAZER - UMA REVISÃO.

OBJECTIVE: To carry out a review about Prader-Willi Syndrome based on the most recent data about the subject and to give recommendation for the general pediatricians for early diagnoses and follow-up. DATA SOURCES: Scientific articles in the PubMed and SciELO databases. The research was not limited to a specific time period and included all articles in such databases. DATA SYNTHESIS: The Prader-Willi Syndrome (PWS) is a rare genetic disorder resulting from the loss of imprinted gene expression within the paternal chromosome 15q11-q13. PWS is characterized by endocrine abnormalities, such as growth hormone (GH) deficiency, obesity, central adrenal insufficiency, hypothyroidism, hypogonadism and complex behavioral and intellectual difficulties. PWS individuals also may present other comorbidities, such as sleep disorders, scoliosis, constipation, dental issues and coagulation disorders. The follow-up protocol of the Children's Institute at Universidade de São Paulo is based on four main pillars: diet, exercise, recombinant human growth hormone (rhGH) therapy and behavioral and cognitive issues. The diet must include a caloric restriction of 900 kcal/day, according to the Prader-Willi Eating Pyramid and exercise plan is focused on daily aerobic exercises and postural therapy. The rhGH therapy is highly recommended by the international scientific literature and must be started as soon as the diagnostic is made. The management of behavioral issues is based on strategies to establish routine and rules. CONCLUSIONS: If the general pediatrician becomes more familiar with PWS, the diagnosis and treatment will start earlier, which is essential to improve the quality of life and care for these individuals.

OBJETIVO: Realizar uma revisão sobre a Síndrome de Prader-Willi (SPW) com base nas publicações mais recentes e fornecer recomendações ao pediatra geral para diagnóstico precoce e seguimento. FONTE DE DADOS: Artigos publicados nas bases Pubmed e SciELO. A pesquisa não foi limitada a um período e incluiu todos os artigos das bases de dados. SÍNTESE DOS DADOS: A SPW é uma síndrome genética rara, resultante da perda do imprinting gênico expresso no cromossomo paterno 15q11-q13, sendo caracterizada por alterações endocrinológicas, como deficiência de hormônio de crescimento, obesidade, insuficiência adrenal central, hipotireoidismo, hipogonadismo, além de alterações comportamentais e déficit intelectual. Há outras comorbidades associadas, como distúrbios de sono, escoliose, constipação, problemas dentários e alterações de coagulação. O protocolo de seguimento da SPW do Instituto da Criança da Universidade de São Paulo se baseia em quarto pilares principais: dieta, exercício físico, terapia com hormônio de crescimento humano recombinante (rhGH) e manejo comportamental e cognitivo. A dieta deve ser restrita a 900 kcal/dia, de acordo com a Pirâmide Alimentar do Prader-Willi, e o exercício físico deve ser diário, aeróbico e postural. A terapia com rhGH é fortemente recomendada pela literatura científica internacional e deve ser iniciada assim que for realizado o diagnóstico da síndrome. O manejo do comportamento é realizado com estratégias para estabelecer rotina e regras. CONCLUSÕES: Se a SPW se tornar mais familiar ao pediatra geral, o diagnóstico e o tratamento começarão mais precocemente, o que irá melhorar a qualidade de vida e os cuidados desses pacientes.

Síndrome de prader willi: o que o pediatra geral deve fazer - uma revisão / Prader-willi syndrome: what is the general pediatrician supposed to do? - a review

RESUMO Objetivo: Realizar uma revisão sobre a Síndrome de Prader-Willi (SPW) com base nas publicações mais recentes e fornecer recomendações ao pediatra geral para diagnóstico precoce e seguimento. Fonte de dados: Artigos publicados nas bases Pubmed e SciELO. A pesquisa não foi limitada a um período e incluiu todos os artigos das bases de dados. Síntese dos dados: A SPW é uma síndrome genética rara, resultante da perda do imprinting gênico expresso no cromossomo paterno 15q11-q13, sendo caracterizada por alterações endocrinológicas, como deficiência de hormônio de crescimento, obesidade, insuficiência adrenal central, hipotireoidismo, hipogonadismo, além de alterações comportamentais e déficit intelectual. Há outras comorbidades associadas, como distúrbios de sono, escoliose, constipação, problemas dentários e alterações de coagulação. O protocolo de seguimento da SPW do Instituto da Criança da Universidade de São Paulo se baseia em quarto pilares principais: dieta, exercício físico, terapia com hormônio de crescimento humano recombinante (rhGH) e manejo comportamental e cognitivo. A dieta deve ser restrita a 900 kcal/dia, de acordo com a Pirâmide Alimentar do Prader-Willi, e o exercício físico deve ser diário, aeróbico e postural. A terapia com rhGH é fortemente recomendada pela literatura científica internacional e deve ser iniciada assim que for realizado o diagnóstico da síndrome. O manejo do comportamento é realizado com estratégias para estabelecer rotina e regras. Conclusões: Se a SPW se tornar mais familiar ao pediatra geral, o diagnóstico e o tratamento começarão mais precocemente, o que irá melhorar a qualidade de vida e os cuidados desses pacientes.

ABSTRACT Objective: To carry out a review about Prader-Willi Syndrome based on the most recent data about the subject and to give recommendation for the general pediatricians for early diagnoses and follow-up. Data sources: Scientific articles in the PubMed and SciELO databases. The research was not limited to a specific time period and included all articles in such databases. Data synthesis: The Prader-Willi Syndrome (PWS) is a rare genetic disorder resulting from the loss of imprinted gene expression within the paternal chromosome 15q11-q13. PWS is characterized by endocrine abnormalities, such as growth hormone (GH) deficiency, obesity, central adrenal insufficiency, hypothyroidism, hypogonadism and complex behavioral and intellectual difficulties. PWS individuals also may present other comorbidities, such as sleep disorders, scoliosis, constipation, dental issues and coagulation disorders. The follow-up protocol of the Children's Institute at Universidade de São Paulo is based on four main pillars: diet, exercise, recombinant human growth hormone (rhGH) therapy and behavioral and cognitive issues. The diet must include a caloric restriction of 900 kcal/day, according to the Prader-Willi Eating Pyramid and exercise plan is focused on daily aerobic exercises and postural therapy. The rhGH therapy is highly recommended by the international scientific literature and must be started as soon as the diagnostic is made. The management of behavioral issues is based on strategies to establish routine and rules. Conclusions: If the general pediatrician becomes more familiar with PWS, the diagnosis and treatment will start earlier, which is essential to improve the quality of life and care for these individuals.

Physiological adaptation after a 12-week physical activity program for patients with Prader-Willi syndrome: two case reports.

BACKGROUND: Physical activity programs are a powerful tool against several diseases including obesity and their comorbidities. Prader-Willi syndrome is the most common genetic disease associated with obesity, and brings with it behavioral and emotional problems that need complex management. Research into the effect of physical activity programs on Prader-Willi syndrome is limited and it is frequently argued that if a physical activity program is too complex, the participants are more likely to drop out. Therefore, in this study, we assessed the physiological adaptation effect of a physical activity program with increasing complexity and load, in a boy and a girl with Prader-Willi syndrome by assessing changes in lipid profile, body composition, and physical fitness parameters. CASE PRESENTATION: Case 1 was an 11-year-old girl, mixed race (brown), with an intelligence quotient of 68, 52.0 % body fat, and a body mass index of 45.3 kg/m(2). The Prader-Willi syndrome diagnosis was made when she was 5-years old and was found to be due to an imprinting genomic defect. Case 2 was a 14-year-old boy, mixed race (brown), with an intelligence quotient of 74, 48.8 % body fat, and a body mass index of 37.3 kg/m(2). The diagnosis was made when he was 10-years old and was found to be caused by gene deletion. Both participants presented physical characteristics and behavior problems typical of Prader-Willi syndrome. Case 2 presented high blood pressure, high cholesterol and sleep apnea and had to use continuous positive airway pressure to sleep. Both participants were assessed for 12 weeks (three times a week) using a physical activity program designed to improve strength and muscle hypertrophy. The work load was progressively adjusted as necessary and new exercises were added to the program. Prior to the program, the participants' parents received instructions about managing problem behavior and advice about nutrition. CONCLUSIONS: After physical activity program several health markers assessed by biological tests and parental report had improved in both participants. The participants positively accepted the adaptations made to the physical activity program during the study. More studies are necessary to assess the benefits of physical activity in the Prader-Willi syndrome population.

The High Direct Medical Costs of Prader-Willi Syndrome.

OBJECTIVE: To assess medical resource utilization associated with Prader-Willi syndrome (PWS) in the US, hypothesized to be greater relative to a matched control group without PWS. STUDY DESIGN: We used a retrospective case-matched control design and longitudinal US administrative claims data (MarketScan) during a 5-year enrollment period (2009-2014). Patients with PWS were identified by Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 759.81. Controls were matched on age, sex, and payer type. Outcomes included total, outpatient, inpatient and prescription costs. RESULTS: After matching and application of inclusion/exclusion criteria, we identified 2030 patients with PWS (1161 commercial, 38 Medicare supplemental, and 831 Medicaid). Commercially insured patients with PWS (median age 10 years) had 8.8-times greater total annual direct medical costs than their counterparts without PWS (median age 10 years: median costs $14 907 vs $819; P < .0001; mean costs: $28 712 vs $3246). Outpatient care comprised the largest portion of medical resource utilization for enrollees with and without PWS (median $5605 vs $675; P < .0001; mean $11 032 vs $1804), followed by mean annual inpatient and medication costs, which were $10 879 vs $1015 (P < .001) and $6801 vs $428 (P < .001), respectively. Total annual direct medical costs were ∼42% greater for Medicaid-insured patients with PWS than their commercially insured counterparts, an increase partly explained by claims for Medicaid Waiver day and residential habilitation. CONCLUSION: Direct medical resource utilization was considerably greater among patients with PWS than members without the condition. This study provides a first step toward quantifying the financial burden of PWS posed to individuals, families, and society.

Síndrome de Prader-Willi: criterio y guía para la atención odontopediátrica / Prader-Willi syndrome: criteria and guidelines for the pediatric dental care

El síndrome de Prader-Willi (SPW) es una enfermedad rara (incidencia 1:15.000), de causa genética, debido a una deleción del cromosoma 15 paterno en la región 15q 11-q13. Presenta alteraciones a nivel del hipotálamo con manifestaciones clínicas típicas, tales como hipotonía, hipogonadismo, facies típica y retraso mental que permiten su diagnóstico. El pronóstico de esta patología suele ser favorable si existe un adecuado manejo en la alimentación y un ambiente familiar con contención. Los odontólogos cumplen un rol fundamental en el mantenimienot y prevención de la salud bucal. El trabajo de interdisciplina es uno de los pilares fundamentales para un correcto abordaje y tratamiento odontológico, con el objetivo final de lograr la salud bucal que redundará en la salud sistémica de estas personas. En una unidad de atención odontológica especializada para niños portadores de discapacidad y riesgo médico se han atendido 16 pacientes durante los últimos 6 años, habiéndose confeccionado una guía de atención odontológica para pacientes con SPW basada en el plan de tratamiento odontopediátrico personalizado que tendrá en cuenta los signos y sintomatología sistémica y en especial las características bucodentales. De la atención clínica surgió la necesidad de realizar estudios específicos en la saliva de estos niños, por su característica especial, los cuales fueron realizados en interrelación con la universidad relacionada a la unidad de atención de pacientes especiales.

Morbid obesity in an adolescent with Prader-Willi syndrome.

Prader-Willi syndrome is an uncommon multisystem genetic disorder caused by defects of chromosome 15 (15qll-ql3), often due to deletions or uniparental disomy The syndrome is characterized by neonatal hypotonia, dysmorphic facial features, short stature, motor and mental disabilities, behavioral changes, hyperphagia, precocious obesity and hypogonadotropic hypogonadism. We present a 17 year-old woman, with a previous genetic diagnosis of Prader-Willi syndrome and BMI of 74 Kg/m(2), that was admitted in anasarca, with marked cyanosis, dyspnea and oliguria. She presented high levels of blood urea, creatinine and aminotransferases, in addition to hyperkalemia and hyperuricemia. She had been in regular use of fluoxetine during the last six months, and evolved with severe high blood pressure and respiratory failure, which needed intensive care support. Moreover, sequels and clear signs of recent self-injuries were observed in her trunk, forearms and hands. The findings of morbid obesity, anasarca, self-injury, hyperuricemia and hypoxemia in Prader-Willi syndrome are emphasized.

Morbid obesity in an adolescent with Prader-Willi syndrome / Obesidad mórbida en una adolescente con síndrome de Prader-Willi

Prader- Willi syndrome is an uncommon multisystem genetic disorder caused by defects of chromosome 15 (15qll-ql3), often due to deletions or uniparental disomy The syndrome is characterized by neonatal hypotonia, dysmorphic facial features, short stature, motor and mental disabilities, behavioral changes, hyperphagia, precocious obesity and hypogonadotropic hypogonadism. We present a 17 year-old woman, with a previous genetic diagnosis of Prader-Willi syndrome and BMI of 74 Kg/m², that was admitted in anasarca, with marked cyanosis, dyspnea and oliguria. She presented high levels ofblood urea, creatinine and aminotransferases, in addition to hyperkalemia and hyperuricemia. She had been in regular use of fluoxetine during the last six months, and evolved with severe high bloodpressure and respiratory failure, which needed intensive care support. Moreover, sequéis and clear signs of recent selfinjuries were observed in her trunk, forearms and hands. The findings of morbid obesity, anasarca, self-injury, hyperuricemia and hypoxemia in Prader- Willi syndrome are emphasized.

El síndrome de Prader-Willi es un desorden multisistémico infrecuente causado por defectos genéticos del cromosoma 15 (15qll-ql3), debido a deleciones o disomía uniparental. Se caracteriza por hipotonía neonatal, dismorfias faciales, baja estatura, incapacidades motoras y mentales, problemas conductuales, hiperfagia, obesidad precoz e hipogonadismo hipogonadotrófico. Presentamos una mujer de 17 años, con IMC de 74 Kg/m² con diagnóstico genético previo del síndrome que ingresó con anasarca, intensa cianosis, disnea y oliguria. Presentaba elevación plasmática de urea, creatinina y aminotransferasas, asociadas con hiperkalemia e hiperuricemia. Había utilizado regularmente ñuoxetina durante los seis meses precedentes y evolucionó con hipertensión arterial severa e insuficiencia respiratoria, que requirieron de cuidados intensivos. Además, se constataron cicatrices y claras señales de automutilación reciente en su tronco, antebrazos y manos. Se destacan los hallazgos de obesidad mórbida, anasarca, automutilación, hiperuricemia e hipoxemia en el síndrome de Prader-Willi.

Impronta genómica en el síndrome de Prader-Willi y en el síndrome de Angelman / Genetic imprinting in the Prader-Willi and Angelman syndromes

Los síndromes de Angelman y Prader-Willi son desórdenes del neurocomportamiento con manifestaciones clínicas diferentes y constituyen el mejor ejemplo del concepto de impronta genómica. Se encuentran asociados con deficiencias maternas y paternas de una misma región en el cromosoma 15q11-q13, respectivamente. Los pacientes con síndrome de Prader-Willi presentan hipotonía muscular al nacimiento, obesidad, talla baja, retraso psicomotor e hipogonadismo; la facies es peculiar. El síndrome de Angelman se caracteriza por microbraquicefalia, pelo delgado y claro, hipoplasia maxilar, ojos hundidos, boca grande con protrusión lingual y prognatismo; el retraso psicomotor es severo, neurológicamente presentan ataxia, movimientos como ®marioneta¼ y ausencia del lenguaje; la mayoría de los pacientes presenta convulsiones, electroencefalograma anormal y paroxismos de risa. El pronóstico de ambas enfermedades es bueno si se evitan las complicaciones

Síndrome de Prader-Willi / Prader-Willy Syndrome

A Síndrome de Prader-Willi é uma doença rara, congênita, que acomete 1 a cada 15 mil nascimentos, caracterizada por hipogonadismo, hiperfagia com obesidade mórbida, baixa estatura, retardo mental, fácies dismórfica, sendo originada de uma anormalidade no braço longo do cromossomo 15 no locus 15q 11-13 de origem paterna. Relata-se caso de Síndrome de Prader-Willi, com revisäo da literatura, apresentando características clínicas, genéticas, dietéticas, metabólicas e tratamento