Title: Integrating Consistent Individualized Carbohydrate-Controlled Anti- Inflammatory Nutritional Plan (C-ICAN) in the Management of Prader-Willi Syndrome: A Case Report. Prader–Willi syndrome (PWS) is a rare genet...Title: Integrating Consistent Individualized Carbohydrate-Controlled Anti- Inflammatory Nutritional Plan (C-ICAN) in the Management of Prader-Willi Syndrome: A Case Report. Prader–Willi syndrome (PWS) is a rare genetic disorder caused by a loss of function of specific genes on chromosome 15. Patients with this disease present unique challenges in management, particularly regarding obesity and nutritional regulation as the disease symptoms change depending on the age of the patient and the phase of the disease. These challenges pose critical stressors to caregivers and their families. We present a case report of a 5-year-old Caucasian male diagnosed with PWS, exhibiting failure to thrive and uncontrolled weight gain. His caregiver was his elderly grandmother who, by her own admission, was ill-equipped to deal with the patient’s physical symptoms and his behavior in response to dietary restrictions. Through a multidisciplinary approach involving medical nutrition therapy (MNT) involving the implementation of a Consistent Individualized Carbohydrate-Controlled Anti-Inflammatory Nutritional plan (C-ICAN), growth hormone supplementation, and behavioral interventions patient markedly improved physically and emotionally.展开更多
Prader-Willi Syndrome （PWS） is a genetic disorder that is difficult to detect, particularly at an early age. PWS is caused by disruption of normal, epigenetically controlled gene function in the chromosome 15q11-q13...Prader-Willi Syndrome （PWS） is a genetic disorder that is difficult to detect, particularly at an early age. PWS is caused by disruption of normal, epigenetically controlled gene function in the chromosome 15q11-q13 region. Clinical symptoms are difficult to diagnose in infants and only become clearer at later ages as the patients develop hyperphagia and morbid obesity. Molecular genetic tests are able to definitively diagnose PWS and allow early diagnosis of the syndrome. High resolution cytogenetic testing, methylation-specific PCR （MS-PCR）, and linkage analysis are routinely used to diagnose PWS. To establish a linkage analysis method for Chinese patients, this study identified a useful set of STR markers in the typical PWS deletion and adjacent area, for linkage analysis in two Chinese families with PWS offspring. Using this method, the authors confn＇rned that one patient had a paternal deletion in chromosome 15q 11-q 13 and the other patient had maternal uniparental heterodisomy of chromosome 15. MS -PCR and high resolution chromosome G-banding also confirmed this diagnosis. This linkage analysis method can detect both deletion and uniparental disomy, thus providing valuable information for genetic counseling and the opportunity to analyze the relationship between the genotype and phenotype of PWS.展开更多
Objective Prader-Willi Sydrome （PWS） is a human disorder related to genomic imprinting defect on 15ql 1-13. It is characterized by a series of classic features such as hypotonia, hyperphagia, obesity, osteoporosis, ...Objective Prader-Willi Sydrome （PWS） is a human disorder related to genomic imprinting defect on 15ql 1-13. It is characterized by a series of classic features such as hypotonia, hyperphagia, obesity, osteoporosis, typical facial and body dysmorphosis, hypogonadism, mental and behaviour disorders. Our study was designed to precisely detect the microdeletions, which accounts for 65%-70% of the PWS. Methods Physical and laboratory examinations were firstly performed to diagnose PWS clinically, and to discover novel clinical features. Then the patient was screened with bisulfite-specific sequencing and precisely delineated through high-density array CGH. Results With the bisulfite-specific sequencing, the detected CpG island in the PWS critical region was found homozygously hypermethylated. Then with array CGH, a 2.22 Mb type II microdeletion was detected, covering a region from MKRN3, MAGEL2, NDN, PWRN2, PWRN1, Cl2orf2, SNURF-SNRPN, C/D snoRNAs, to distal of UBE3A. Conclusions Array CGH, after the fast screening of Bisulfite-specific sequencing, is a feasible and precise method to detect microdeletions in PWS patients. A novel feature of metacarpophalangeal joint rigidity was also presented, which is the first time reported in PWS.展开更多
BACKGROUND Sleep-disordered breathing,including hypoventilation and obstructive sleep apnea,is often observed in Prader-Willi syndrome(PWS).Particularly in adolescence,scoliosis causes a progressive restrictive pulmon...BACKGROUND Sleep-disordered breathing,including hypoventilation and obstructive sleep apnea,is often observed in Prader-Willi syndrome(PWS).Particularly in adolescence,scoliosis causes a progressive restrictive pulmonary pattern,leading to hypoventilation,so timely corrective surgery is required.However,the effect is controversial.In addition,since mental retardation of PWS,patient effort-based respiratory tests may be less reliable.So far,no studies have accurately reported on the comparison of respiratory function before and after corrective surgery,and appropriate respiratory function measurement method in PWS.CASE SUMMARY We present two cases of adolescent PWS with typical characteristics,including obesity,mental retardation,and scoliosis.Two boys,aged 12 and 13,diagnosed with PWS,both underwent scoliosis correction surgery.Before and immediately after surgery,arterial blood tests showed no abnormalities and no respiratory symptoms occurred.However,after 6-7 mo,both patients complained of daytime sleepiness,difficulty sleeping at night,dyspnea on exertion,and showed cyanosis.Hypercapnia and hypoxia were confirmed by polysomnography and transcutaneous CO2 monitoring during sleep and were diagnosed with obstructive sleep apnea and alveolar hypoventilation.It was corrected by nighttime noninvasive ventilation application and normal findings of arterial blood gas were maintained after 6-8 mo follow-up.CONCLUSION Even after scoliosis surgery,“periodic”monitoring of respiratory failure with an“objective”test method is needed for timely respiratory support.展开更多
Relentless pursuit of food is a major characteristic of Prader-Willi Syndrome (PWS). We observed voluntary fasting among PWS individuals during a religious fast. Understanding the mechanisms involved in successful fas...Relentless pursuit of food is a major characteristic of Prader-Willi Syndrome (PWS). We observed voluntary fasting among PWS individuals during a religious fast. Understanding the mechanisms involved in successful fasting could be an important contribution in developing more effective treatment of this syndrome. We conducted a prospective study to assess whether genotype, motivational attitudes (e.g. religiosity) and control patterns (e.g. different eating habits) would correlate with ability to fast. Among all individuals with PWS in Israel, 32 met inclusion criteria. Prior to the fast, each participant and parents/caregivers were interviewed for demographic, medical and behavioral data and completed questionnaires assessing motivational and control factors. 22 participants completed the fast. This ability was not accounted for by religiosity, demographic, medical variables or genetic subtype. This prospective study documents that in spite of extreme hyperphagia, adolescents and adults with PWS can voluntarily abstain from food for 25 hours;our findings suggest that they are able to activate mechanisms which improve their control of eating for a longer period than expected. The observation that the degree of religiosity did not impact on the ability to fast suggests that these mechanisms may be applicable to a wider range of circumstances and populations. The ability for self-control under special circumstances deserves further study;it may be relevant to other types of severe obesity and possibly lead to improved methods of behavioral modification.展开更多
BACKGROUND As research on diabetes continues to advance,more complex classifications of this disease have emerged,revealing the existence of special types of diabetes,and many of these patients are prone to misdiagnos...BACKGROUND As research on diabetes continues to advance,more complex classifications of this disease have emerged,revealing the existence of special types of diabetes,and many of these patients are prone to misdiagnosis and underdiagnosis,leading to treatment delays and increased health care costs.The purpose of this study was to identify four causes of secondary diabetes.CASE SUMMARY Secondary diabetes can be caused by various factors,some of which are often overlooked.These factors include genetic defects,autoimmune disorders,and diabetes induced by tumours.This paper describes four types of secondary diabetes caused by Williams–Beuren syndrome,Prader–Willi syndrome,pituitary adenoma,and IgG4-related diseases.These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity,often leading to their neglect in clinical practice.In comparison to regular diabetes patients,the four individuals described here exhibited distinct characteristics.Standard hypoglycaemic treatments failed to effectively control the disease.Subsequently,a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes.Upon addressing the primary condition,such as excising a pituitary adenoma,providing glucocorticoid supplementation,and implementing symptomatic treatments,all patients experienced a considerable decrease in blood glucose levels,which were subsequently maintained within a stable range.Furthermore,other accompanying symptoms improved.CONCLUSION Rare diseases causing secondary diabetes are often not considered in the diag-nosis of diabetes.Therefore,it is crucial to conduct genetic tests,antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition,ultimately improving patient outcomes.展开更多
Background Recombinant human growth hormone(rhGH)therapy has shown to improve height and body composition in children with Prader–Willi syndrome(PWS),the evidence of early rhGH treatment on motor and mental developme...Background Recombinant human growth hormone(rhGH)therapy has shown to improve height and body composition in children with Prader–Willi syndrome(PWS),the evidence of early rhGH treatment on motor and mental development is still accumulating.This study explored the time effect on psychomotor development,anthropometric indexes,and safety for infants and young children with PWS.Methods A phase 3,single-arm,multicenter,self-controlled study was conducted in six sites.Patients received rhGH at 0.5 mg/m2/day for first four weeks,and 1 mg/m2/day thereafter for up to 52 weeks.Motor development was measured using Peabody Developmental Motor Scales-second edition,mental development using Griffiths Development Scales-Chinese(GDS-C).Height standard deviation score(SDS),body weight SDS,and body mass index(BMI)SDS were also assessed.Results Thirty-five patients were enrolled totally.Significant improvements were observed in height,body weight,and BMI SDS at week 52;GDS-C score showed significant improvement in general quotient(GQ)and sub-quotients.In a linear regression analysis,total motor quotient(TMQ),gross motor quotient(GMQ),and fine motor quotient were negatively correlated with age;however,treatment may attenuate deterioration of TMQ and GMQ.Changes in GQ and locomotor sub-quotient in<9-month group were significantly higher than≥9-month group.Mild to moderate severity adverse drug reactions were reported in six patients.Conclusion Fifty-two-week treatment with rhGH improved growth,BMI,mental development,and lessened the deterioration of motor function in infants and young children with PWS.Improved mental development was more pronounced when instituted in patients<9 months old.展开更多
Prader-Willi syndrome （PWS） is an important, well-recognized syndromic form of neurodevelopmental disorder. The incidence is about 1 in 15,000-25,000 live births, and it affects both males and females （Vogels et al...Prader-Willi syndrome （PWS） is an important, well-recognized syndromic form of neurodevelopmental disorder. The incidence is about 1 in 15,000-25,000 live births, and it affects both males and females （Vogels et al., 2004）. The underlying genetic defects occur at an imprinted region on chromosome 15ql 1-13.展开更多
Background This study aimed to measure quality of life(QOL)in primary caregivers of young childrenwith Prader-Willi syndrome(PWS).Methods The caregivers of 32 children aged from 6.1 to 71.2 months completed the Chines...Background This study aimed to measure quality of life(QOL)in primary caregivers of young childrenwith Prader-Willi syndrome(PWS).Methods The caregivers of 32 children aged from 6.1 to 71.2 months completed the Chinese version of the World Health Organization Quality of Life-BREF(WHOQOL-BREF).We also evaluated the social adaption capacity of these children with Infants-Junior Middle School Students'Social-Life Abilities Scale.Correlation test was used to explore the related factors to caregivers'QOL.Results Caregivers of young children with PWS had significantly lower QOL.The correlation analyses revealed that caregivers'QOL was lower in children with young age,combined diseases or symptoms or poor social adaption,or caregivers having concerns about the child.Conclusions Rearing a chilld with PWS may lead to decreased QOL.Psychological status of caregivers should be highlighted and social support should be given to families with PWS children.展开更多
Background:Epilepsy associated with Prader-Willi syndrome(PWS)represents an early and important complication,often not clearly reported and described in the literature.Consequently,there are controversial data about t...Background:Epilepsy associated with Prader-Willi syndrome(PWS)represents an early and important complication,often not clearly reported and described in the literature.Consequently,there are controversial data about the clinical characteristics of epilepsy and electroencephalographic(EEG)abnormalities found in these patients.Data sources:Based on recent original publications,we have reviewed the different types of seizures and EEG findings in PWS patients,the response to antiepileptic treatment,and the prognosis of epilepsy.Results:The frequency of epilepsy in PWS patients ranges from 4%to 26%.The types of seizure include generalized tonic-clonic seizures,complex partial seizures,atypical absence,staring spells,and myoclonic,tonic and hemiclonic seizures,but the most frequent type is focal epilepsy.Status epilepticus has never been reported.EEG abnormalities are not typical but variable in different patients.However,generalized and focal discharges are the most frequently reported findings.There is no evidence of relationship between the course of epilepsy and frequency,morphology and spread of EEG discharges.However,epilepsy in PWS patients is usually responsive to antiepileptic monotherapy with rapid seizure control and a good outcome.Conclusions:The frequency of epilepsy is higher in PWS patients than in general populations and this complication can be a challenge for the clinicians of these patients.Prospective studies are needed to confirm the good long-term prognosis.展开更多
Prader—Willi syndrome(PWS)is a rare congenital disease with genetic alterations in chromosome 15.Although genetic disorders and DNA methylation abnormalities involved in PWS have been investigated to a significant de...Prader—Willi syndrome(PWS)is a rare congenital disease with genetic alterations in chromosome 15.Although genetic disorders and DNA methylation abnormalities involved in PWS have been investigated to a significant degree,other anomalies such as those in erythrocytes may occur and these have not been clearly elucidated.In the present study,we uncovered slight anemia in children with PWS that was associated with increased red blood cell(RBC)distribution width(RDW)and contrarily reduced hematocrit(HCT)values.Intriguingly,the increased ratio in RDW to HCT allowed sufficient differentiation between the PWS patients from the healthy controls and,importantly,with individuals exhibiting conventional obesity.Further morphologic examinations revealed a significant deformity in erythrocytes and mild hemolysis in PWS patients.Comprehensive mechanistic investigations unveiled compromised membrane skeletal assembly and membrane lipid composition,and revealed a reduced F-actin/G-actin ratio in PWS patients.We ascribed these phenotypic changes in erythrocytes to the observed genetic defects,including DNA methylation abnormalities.Our collective data allowed us to uncover RBC deformation in children with PWS,and this may constitute an auxiliary indicator of PWS in early childhood.展开更多
Abnormal serotonin 2C receptor (5HTR2C) alternative splicing and RNA editing are involved in the etiology of pain disorders. Functional 5HTR2C can only be generated when alternative exon Vb is included within the mRNA...Abnormal serotonin 2C receptor (5HTR2C) alternative splicing and RNA editing are involved in the etiology of pain disorders. Functional 5HTR2C can only be generated when alternative exon Vb is included within the mRNA;the small nucleolar RNA RBII-52 is complementary to exon Vb and promotes its inclusion. The expression of HBII-52 (the human equivalent of RBII-52) is reduced in Prader-Willi syndrome, patients of which have a high pain threshold. Here, we measured the pain threshold in a rat model of orofacial neuropathic pain and related it to the expression levels of wild-type and variant 5HTR2C and RBII-52. We generated an infraorbital nerve loose ligation model of neuropathic pain in rats and measured the pain threshold of the animals using mechanical stimulation with von Frey filaments. We then sacrificed the animals and examined the RNA levels of 5HTR2C and RBII-52 in the cervical spinal cord by real-time PCR. On post-injury day 28, pain threshold values in injured rats were significantly lower than in sham-operated or na?ve animals. The levels of total and exon Vb-skipped 5HTR2C mRNA were significantly lower in injured rats than in that sham-operated or na?ve rats, and the ratio of exon Vb-skipped 5HTR2C to total 5HTR2C was significantly higher. There were no significant differences in RBII-52 expression among the groups. Our data suggest that neuropathic pain induces serotonergic dysfunction mediated by 5HTR2C alternative splicing. 5HTR2C might be subject to complicated and fine regulation both by RNA editing and by alternative splicing.展开更多
Background Obesity is a multifactorial chronic disease with a high,increasing worldwide prevalence.Genetic causes account for 7%of the cases in children with extreme obesity.Data sources This narrative review was cond...Background Obesity is a multifactorial chronic disease with a high,increasing worldwide prevalence.Genetic causes account for 7%of the cases in children with extreme obesity.Data sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 articles.The search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case reports.Results The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight.However,several important aspects of the pathophysiology of obesity remain unknown.Genetic causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose.There are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric surgery.Conclusions Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.展开更多
文摘Title: Integrating Consistent Individualized Carbohydrate-Controlled Anti- Inflammatory Nutritional Plan (C-ICAN) in the Management of Prader-Willi Syndrome: A Case Report. Prader–Willi syndrome (PWS) is a rare genetic disorder caused by a loss of function of specific genes on chromosome 15. Patients with this disease present unique challenges in management, particularly regarding obesity and nutritional regulation as the disease symptoms change depending on the age of the patient and the phase of the disease. These challenges pose critical stressors to caregivers and their families. We present a case report of a 5-year-old Caucasian male diagnosed with PWS, exhibiting failure to thrive and uncontrolled weight gain. His caregiver was his elderly grandmother who, by her own admission, was ill-equipped to deal with the patient’s physical symptoms and his behavior in response to dietary restrictions. Through a multidisciplinary approach involving medical nutrition therapy (MNT) involving the implementation of a Consistent Individualized Carbohydrate-Controlled Anti-Inflammatory Nutritional plan (C-ICAN), growth hormone supplementation, and behavioral interventions patient markedly improved physically and emotionally.
文摘Prader-Willi Syndrome （PWS） is a genetic disorder that is difficult to detect, particularly at an early age. PWS is caused by disruption of normal, epigenetically controlled gene function in the chromosome 15q11-q13 region. Clinical symptoms are difficult to diagnose in infants and only become clearer at later ages as the patients develop hyperphagia and morbid obesity. Molecular genetic tests are able to definitively diagnose PWS and allow early diagnosis of the syndrome. High resolution cytogenetic testing, methylation-specific PCR （MS-PCR）, and linkage analysis are routinely used to diagnose PWS. To establish a linkage analysis method for Chinese patients, this study identified a useful set of STR markers in the typical PWS deletion and adjacent area, for linkage analysis in two Chinese families with PWS offspring. Using this method, the authors confn＇rned that one patient had a paternal deletion in chromosome 15q 11-q 13 and the other patient had maternal uniparental heterodisomy of chromosome 15. MS -PCR and high resolution chromosome G-banding also confirmed this diagnosis. This linkage analysis method can detect both deletion and uniparental disomy, thus providing valuable information for genetic counseling and the opportunity to analyze the relationship between the genotype and phenotype of PWS.
基金supported by grants from National 973 Program(2006CB503901)Shanghai Key Laboratory of Diabetes Mellitus(08DZ2230200)+1 种基金Major Program of Shanghai Municipality for Basic Research(08dj 1400601)Program for Outstanding Medical Academic Leader in Shanghai (LJ06010).
文摘Objective Prader-Willi Sydrome （PWS） is a human disorder related to genomic imprinting defect on 15ql 1-13. It is characterized by a series of classic features such as hypotonia, hyperphagia, obesity, osteoporosis, typical facial and body dysmorphosis, hypogonadism, mental and behaviour disorders. Our study was designed to precisely detect the microdeletions, which accounts for 65%-70% of the PWS. Methods Physical and laboratory examinations were firstly performed to diagnose PWS clinically, and to discover novel clinical features. Then the patient was screened with bisulfite-specific sequencing and precisely delineated through high-density array CGH. Results With the bisulfite-specific sequencing, the detected CpG island in the PWS critical region was found homozygously hypermethylated. Then with array CGH, a 2.22 Mb type II microdeletion was detected, covering a region from MKRN3, MAGEL2, NDN, PWRN2, PWRN1, Cl2orf2, SNURF-SNRPN, C/D snoRNAs, to distal of UBE3A. Conclusions Array CGH, after the fast screening of Bisulfite-specific sequencing, is a feasible and precise method to detect microdeletions in PWS patients. A novel feature of metacarpophalangeal joint rigidity was also presented, which is the first time reported in PWS.
文摘BACKGROUND Sleep-disordered breathing,including hypoventilation and obstructive sleep apnea,is often observed in Prader-Willi syndrome(PWS).Particularly in adolescence,scoliosis causes a progressive restrictive pulmonary pattern,leading to hypoventilation,so timely corrective surgery is required.However,the effect is controversial.In addition,since mental retardation of PWS,patient effort-based respiratory tests may be less reliable.So far,no studies have accurately reported on the comparison of respiratory function before and after corrective surgery,and appropriate respiratory function measurement method in PWS.CASE SUMMARY We present two cases of adolescent PWS with typical characteristics,including obesity,mental retardation,and scoliosis.Two boys,aged 12 and 13,diagnosed with PWS,both underwent scoliosis correction surgery.Before and immediately after surgery,arterial blood tests showed no abnormalities and no respiratory symptoms occurred.However,after 6-7 mo,both patients complained of daytime sleepiness,difficulty sleeping at night,dyspnea on exertion,and showed cyanosis.Hypercapnia and hypoxia were confirmed by polysomnography and transcutaneous CO2 monitoring during sleep and were diagnosed with obstructive sleep apnea and alveolar hypoventilation.It was corrected by nighttime noninvasive ventilation application and normal findings of arterial blood gas were maintained after 6-8 mo follow-up.CONCLUSION Even after scoliosis surgery,“periodic”monitoring of respiratory failure with an“objective”test method is needed for timely respiratory support.
文摘Relentless pursuit of food is a major characteristic of Prader-Willi Syndrome (PWS). We observed voluntary fasting among PWS individuals during a religious fast. Understanding the mechanisms involved in successful fasting could be an important contribution in developing more effective treatment of this syndrome. We conducted a prospective study to assess whether genotype, motivational attitudes (e.g. religiosity) and control patterns (e.g. different eating habits) would correlate with ability to fast. Among all individuals with PWS in Israel, 32 met inclusion criteria. Prior to the fast, each participant and parents/caregivers were interviewed for demographic, medical and behavioral data and completed questionnaires assessing motivational and control factors. 22 participants completed the fast. This ability was not accounted for by religiosity, demographic, medical variables or genetic subtype. This prospective study documents that in spite of extreme hyperphagia, adolescents and adults with PWS can voluntarily abstain from food for 25 hours;our findings suggest that they are able to activate mechanisms which improve their control of eating for a longer period than expected. The observation that the degree of religiosity did not impact on the ability to fast suggests that these mechanisms may be applicable to a wider range of circumstances and populations. The ability for self-control under special circumstances deserves further study;it may be relevant to other types of severe obesity and possibly lead to improved methods of behavioral modification.
文摘BACKGROUND As research on diabetes continues to advance,more complex classifications of this disease have emerged,revealing the existence of special types of diabetes,and many of these patients are prone to misdiagnosis and underdiagnosis,leading to treatment delays and increased health care costs.The purpose of this study was to identify four causes of secondary diabetes.CASE SUMMARY Secondary diabetes can be caused by various factors,some of which are often overlooked.These factors include genetic defects,autoimmune disorders,and diabetes induced by tumours.This paper describes four types of secondary diabetes caused by Williams–Beuren syndrome,Prader–Willi syndrome,pituitary adenoma,and IgG4-related diseases.These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity,often leading to their neglect in clinical practice.In comparison to regular diabetes patients,the four individuals described here exhibited distinct characteristics.Standard hypoglycaemic treatments failed to effectively control the disease.Subsequently,a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes.Upon addressing the primary condition,such as excising a pituitary adenoma,providing glucocorticoid supplementation,and implementing symptomatic treatments,all patients experienced a considerable decrease in blood glucose levels,which were subsequently maintained within a stable range.Furthermore,other accompanying symptoms improved.CONCLUSION Rare diseases causing secondary diabetes are often not considered in the diag-nosis of diabetes.Therefore,it is crucial to conduct genetic tests,antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition,ultimately improving patient outcomes.
文摘Background Recombinant human growth hormone(rhGH)therapy has shown to improve height and body composition in children with Prader–Willi syndrome(PWS),the evidence of early rhGH treatment on motor and mental development is still accumulating.This study explored the time effect on psychomotor development,anthropometric indexes,and safety for infants and young children with PWS.Methods A phase 3,single-arm,multicenter,self-controlled study was conducted in six sites.Patients received rhGH at 0.5 mg/m2/day for first four weeks,and 1 mg/m2/day thereafter for up to 52 weeks.Motor development was measured using Peabody Developmental Motor Scales-second edition,mental development using Griffiths Development Scales-Chinese(GDS-C).Height standard deviation score(SDS),body weight SDS,and body mass index(BMI)SDS were also assessed.Results Thirty-five patients were enrolled totally.Significant improvements were observed in height,body weight,and BMI SDS at week 52;GDS-C score showed significant improvement in general quotient(GQ)and sub-quotients.In a linear regression analysis,total motor quotient(TMQ),gross motor quotient(GMQ),and fine motor quotient were negatively correlated with age;however,treatment may attenuate deterioration of TMQ and GMQ.Changes in GQ and locomotor sub-quotient in<9-month group were significantly higher than≥9-month group.Mild to moderate severity adverse drug reactions were reported in six patients.Conclusion Fifty-two-week treatment with rhGH improved growth,BMI,mental development,and lessened the deterioration of motor function in infants and young children with PWS.Improved mental development was more pronounced when instituted in patients<9 months old.
文摘Prader-Willi syndrome （PWS） is an important, well-recognized syndromic form of neurodevelopmental disorder. The incidence is about 1 in 15,000-25,000 live births, and it affects both males and females （Vogels et al., 2004）. The underlying genetic defects occur at an imprinted region on chromosome 15ql 1-13.
基金supported by National Natural Science Foundation of China(81371215&81670786)Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health TalentsMedical Health Science and Technology Project of Health Commission of Zhejiang Province(No.2019RC239).
文摘Background This study aimed to measure quality of life(QOL)in primary caregivers of young childrenwith Prader-Willi syndrome(PWS).Methods The caregivers of 32 children aged from 6.1 to 71.2 months completed the Chinese version of the World Health Organization Quality of Life-BREF(WHOQOL-BREF).We also evaluated the social adaption capacity of these children with Infants-Junior Middle School Students'Social-Life Abilities Scale.Correlation test was used to explore the related factors to caregivers'QOL.Results Caregivers of young children with PWS had significantly lower QOL.The correlation analyses revealed that caregivers'QOL was lower in children with young age,combined diseases or symptoms or poor social adaption,or caregivers having concerns about the child.Conclusions Rearing a chilld with PWS may lead to decreased QOL.Psychological status of caregivers should be highlighted and social support should be given to families with PWS children.
文摘Background:Epilepsy associated with Prader-Willi syndrome(PWS)represents an early and important complication,often not clearly reported and described in the literature.Consequently,there are controversial data about the clinical characteristics of epilepsy and electroencephalographic(EEG)abnormalities found in these patients.Data sources:Based on recent original publications,we have reviewed the different types of seizures and EEG findings in PWS patients,the response to antiepileptic treatment,and the prognosis of epilepsy.Results:The frequency of epilepsy in PWS patients ranges from 4%to 26%.The types of seizure include generalized tonic-clonic seizures,complex partial seizures,atypical absence,staring spells,and myoclonic,tonic and hemiclonic seizures,but the most frequent type is focal epilepsy.Status epilepticus has never been reported.EEG abnormalities are not typical but variable in different patients.However,generalized and focal discharges are the most frequently reported findings.There is no evidence of relationship between the course of epilepsy and frequency,morphology and spread of EEG discharges.However,epilepsy in PWS patients is usually responsive to antiepileptic monotherapy with rapid seizure control and a good outcome.Conclusions:The frequency of epilepsy is higher in PWS patients than in general populations and this complication can be a challenge for the clinicians of these patients.Prospective studies are needed to confirm the good long-term prognosis.
基金the National Natural Science Foundation of China(Nos.81974124 and 22076104)the“Outstanding University Driven by Talents”Program and Academic Promotion Program of Shandong First Medical University(Nos.2019LJ007 and 2020LJ002)。
文摘Prader—Willi syndrome(PWS)is a rare congenital disease with genetic alterations in chromosome 15.Although genetic disorders and DNA methylation abnormalities involved in PWS have been investigated to a significant degree,other anomalies such as those in erythrocytes may occur and these have not been clearly elucidated.In the present study,we uncovered slight anemia in children with PWS that was associated with increased red blood cell(RBC)distribution width(RDW)and contrarily reduced hematocrit(HCT)values.Intriguingly,the increased ratio in RDW to HCT allowed sufficient differentiation between the PWS patients from the healthy controls and,importantly,with individuals exhibiting conventional obesity.Further morphologic examinations revealed a significant deformity in erythrocytes and mild hemolysis in PWS patients.Comprehensive mechanistic investigations unveiled compromised membrane skeletal assembly and membrane lipid composition,and revealed a reduced F-actin/G-actin ratio in PWS patients.We ascribed these phenotypic changes in erythrocytes to the observed genetic defects,including DNA methylation abnormalities.Our collective data allowed us to uncover RBC deformation in children with PWS,and this may constitute an auxiliary indicator of PWS in early childhood.
文摘Abnormal serotonin 2C receptor (5HTR2C) alternative splicing and RNA editing are involved in the etiology of pain disorders. Functional 5HTR2C can only be generated when alternative exon Vb is included within the mRNA;the small nucleolar RNA RBII-52 is complementary to exon Vb and promotes its inclusion. The expression of HBII-52 (the human equivalent of RBII-52) is reduced in Prader-Willi syndrome, patients of which have a high pain threshold. Here, we measured the pain threshold in a rat model of orofacial neuropathic pain and related it to the expression levels of wild-type and variant 5HTR2C and RBII-52. We generated an infraorbital nerve loose ligation model of neuropathic pain in rats and measured the pain threshold of the animals using mechanical stimulation with von Frey filaments. We then sacrificed the animals and examined the RNA levels of 5HTR2C and RBII-52 in the cervical spinal cord by real-time PCR. On post-injury day 28, pain threshold values in injured rats were significantly lower than in sham-operated or na?ve animals. The levels of total and exon Vb-skipped 5HTR2C mRNA were significantly lower in injured rats than in that sham-operated or na?ve rats, and the ratio of exon Vb-skipped 5HTR2C to total 5HTR2C was significantly higher. There were no significant differences in RBII-52 expression among the groups. Our data suggest that neuropathic pain induces serotonergic dysfunction mediated by 5HTR2C alternative splicing. 5HTR2C might be subject to complicated and fine regulation both by RNA editing and by alternative splicing.
文摘Background Obesity is a multifactorial chronic disease with a high,increasing worldwide prevalence.Genetic causes account for 7%of the cases in children with extreme obesity.Data sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 articles.The search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case reports.Results The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight.However,several important aspects of the pathophysiology of obesity remain unknown.Genetic causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose.There are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric surgery.Conclusions Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.
