Abstract Obesity is an epidemic disease that can increase the incidence of type 2 diabetes, cardiovascular disease, malignancy, hypertension, and other health problems that affect the musculoskeletal system. There is a complex interaction between obesity and bone metabolism. In children with obesity, the peroxisome proliferator-activated receptor gamma pathway causes the differentiation of mesenchymal stem cells into adipocytes via osteoblasts, in which results in low bone mass and osteoporosis. Systemic inflammation in obesity has negative effects on bone metabolism. An increase in the number and size of adipose tissue and adipocytokines secreted from adipocytes affect the bone mass of the whole body with hormonal and biochemical effects. The skeletal effects of obesity are mediated by higher oxidative stress and increased production of proinflammatory cytokines. Osteoporosis due to obesity has increased morbidity and mortality in recent years, resulting in important health problems in developed and developing countries.
{"title":"Impact of Obesity on Bone Metabolism in Children","authors":"H. Korkmaz, B. Özkan","doi":"10.1515/jpem-2021-0714","DOIUrl":"https://doi.org/10.1515/jpem-2021-0714","url":null,"abstract":"Abstract Obesity is an epidemic disease that can increase the incidence of type 2 diabetes, cardiovascular disease, malignancy, hypertension, and other health problems that affect the musculoskeletal system. There is a complex interaction between obesity and bone metabolism. In children with obesity, the peroxisome proliferator-activated receptor gamma pathway causes the differentiation of mesenchymal stem cells into adipocytes via osteoblasts, in which results in low bone mass and osteoporosis. Systemic inflammation in obesity has negative effects on bone metabolism. An increase in the number and size of adipose tissue and adipocytokines secreted from adipocytes affect the bone mass of the whole body with hormonal and biochemical effects. The skeletal effects of obesity are mediated by higher oxidative stress and increased production of proinflammatory cytokines. Osteoporosis due to obesity has increased morbidity and mortality in recent years, resulting in important health problems in developed and developing countries.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"285 1","pages":"557 - 565"},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76688090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. C. Adiyaman, Julia v.Schnurbein, J. de Laffolie, A. Hahn, R. Siebert, M. Wabitsch, C. Kamrath
Abstract Objectives Congenital generalized lipodystrophies (CGLs) are a heterogeneous group of rare autosomal recessive disorders characterized by near/total absence of body fat. Pathogenic variants in polymerase-I and transcript release factor gene (PTRF), or CAVIN1, is responsible for CGL4. In addition to generalized fat loss, patients with CGL4 were reported to suffer from myopathy, malignant cardiac arrhythmias, gastrointestinal disorders, and skeletal abnormalities. Here we describe the phenotype of a child with CGL4 due to a rare, novel pathogenic variant in the PTRF/CAVIN1 gene and the long-term effects of metreleptin substitution on comorbidities. Case presentation We describe a now 20-year-old female patient. At the age of 14-years, she was referred to the University Clinic because of uncontrolled diabetes with an HbA1c of 9.3%, requiring 2.4 IU insulin/kg total-body-weight to normalize blood glucose, hepatomegaly, and hypertriglyceridemia of 515 mg/dL. Additionally, she was suffering from malignant cardiac arrhythmia, myopathy, and hyperCKemia. In light of these clinical findings, she was diagnosed with CGL due to a rare, novel variant in the PTRF gene, and was started on metreleptin, a synthetic analog of human leptin. After the initiation of metreleptin treatment, insulin therapy could be stopped and improvement of sonographically assessed liver size was observed, even though serum liver function test stayed mildly elevated. Furthermore, a noticeable improvement of the serum triglyceride levels was also seen. Medical care and regular follow-up visits are being carried out by a multi-disciplinary team. Conclusions Although CGL4 is rare, due to its life-threatening comorbidities and the opportunity for an early intervention, it is important that the clinicians should recognise these patients.
摘要目的先天性全身性脂肪营养不良症(CGLs)是一种罕见的常染色体隐性遗传病，其特征是体脂几乎或完全缺失。聚合酶i和转录释放因子基因(PTRF)或CAVIN1的致病变异负责CGL4。除了全身性脂肪减少外，据报道CGL4患者还患有肌病、恶性心律失常、胃肠道疾病和骨骼异常。在这里，我们描述了一名由于PTRF/CAVIN1基因中罕见的新型致病变异而患有CGL4的儿童的表型，以及美曲瘦素替代对合并症的长期影响。我们描述了一位20岁的女性患者。14岁时，因糖尿病未控制，HbA1c为9.3%，需要2.4 IU /kg总体重胰岛素使血糖正常化，肝肥大，高甘油三酯血症为515 mg/dL，被转介到大学诊所。此外，她还患有恶性心律失常、肌病和高血血症。根据这些临床发现，由于PTRF基因的一种罕见的新型变异，她被诊断为CGL，并开始使用美曲瘦素，一种人类瘦素的合成类似物。在美曲瘦素治疗开始后，胰岛素治疗可以停止，超声评估肝大小的改善被观察到，即使血清肝功能测试保持轻度升高。此外，血清甘油三酯水平也有明显改善。一个多学科小组正在进行医疗护理和定期随访。结论:尽管CGL4是罕见的，由于其危及生命的合并症和早期干预的机会，重要的是临床医生应该认识到这些患者。
{"title":"Congenital generalized lipodystrophy type 4 due to a novel PTRF/CAVIN1 pathogenic variant in a child: effects of metreleptin substitution","authors":"S. C. Adiyaman, Julia v.Schnurbein, J. de Laffolie, A. Hahn, R. Siebert, M. Wabitsch, C. Kamrath","doi":"10.1515/jpem-2022-0022","DOIUrl":"https://doi.org/10.1515/jpem-2022-0022","url":null,"abstract":"Abstract Objectives Congenital generalized lipodystrophies (CGLs) are a heterogeneous group of rare autosomal recessive disorders characterized by near/total absence of body fat. Pathogenic variants in polymerase-I and transcript release factor gene (PTRF), or CAVIN1, is responsible for CGL4. In addition to generalized fat loss, patients with CGL4 were reported to suffer from myopathy, malignant cardiac arrhythmias, gastrointestinal disorders, and skeletal abnormalities. Here we describe the phenotype of a child with CGL4 due to a rare, novel pathogenic variant in the PTRF/CAVIN1 gene and the long-term effects of metreleptin substitution on comorbidities. Case presentation We describe a now 20-year-old female patient. At the age of 14-years, she was referred to the University Clinic because of uncontrolled diabetes with an HbA1c of 9.3%, requiring 2.4 IU insulin/kg total-body-weight to normalize blood glucose, hepatomegaly, and hypertriglyceridemia of 515 mg/dL. Additionally, she was suffering from malignant cardiac arrhythmia, myopathy, and hyperCKemia. In light of these clinical findings, she was diagnosed with CGL due to a rare, novel variant in the PTRF gene, and was started on metreleptin, a synthetic analog of human leptin. After the initiation of metreleptin treatment, insulin therapy could be stopped and improvement of sonographically assessed liver size was observed, even though serum liver function test stayed mildly elevated. Furthermore, a noticeable improvement of the serum triglyceride levels was also seen. Medical care and regular follow-up visits are being carried out by a multi-disciplinary team. Conclusions Although CGL4 is rare, due to its life-threatening comorbidities and the opportunity for an early intervention, it is important that the clinicians should recognise these patients.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"208 0 1","pages":"946 - 952"},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84839321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-31DOI: 10.1515/jpem-2022-frontmatter4
{"title":"Frontmatter","authors":"","doi":"10.1515/jpem-2022-frontmatter4","DOIUrl":"https://doi.org/10.1515/jpem-2022-frontmatter4","url":null,"abstract":"","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86668767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Mosca, T. Santos, A. Mendes, Luís F. M. Ribeiro, Joana Freitas, Maria J. R. Oliveira, C. Rocha, Teresa M. S. Borges
Abstract Background Adrenal insufficiency (AI) is a life-threatening condition caused by an impaired secretion of the adrenal glucocorticoid and mineralocorticoid hormones. It comprises a heterogeneous group of primary, secondary and acquired disorders. Presentation differs according to the child’s age, but it usually presents with nonspecific and insidious symptoms and signs. The main purpose of this study was to describe and compare patients with primary or secondary AI. Methods Retrospective analysis of all patients with adrenal insufficiency followed at the Pediatric Endocrinology Unit in a tertiary care Portuguese hospital over the last 30 years. Data on family history, age at the first manifestation and at etiological diagnosis, and clinical presentation (symptoms, signs and laboratory evaluation) was gathered for all patients. Results Twenty-eight patients with AI were included; 67.9% were male, with a median (25th–75th percentile, P25–P75) age of 1 (0.5–36) month at the first presentation. The principal diagnostic categories were panhypopituitarism (42.9%) and congenital adrenal hyperplasia (25%). The most frequent manifestations (75%) were vomiting and weight loss. They were followed for a median (P25–P75) period of 3.5 (0.6–15.5) years. In respect to neurodevelopmental delay and learning difficulties, they were more common in the secondary AI group. Conclusions Despite medical advances, the diagnosis and management of AI remains a challenge, particularly in the pediatric population, and clinicians must have a high index of suspicion. An early identification of AI can prevent a potential lethal outcome, which may result from severe cardiovascular and hemodynamic instability.
{"title":"Pediatric adrenal insufficiency: thirty years experience at a Portuguese hospital","authors":"S. Mosca, T. Santos, A. Mendes, Luís F. M. Ribeiro, Joana Freitas, Maria J. R. Oliveira, C. Rocha, Teresa M. S. Borges","doi":"10.1515/jpem-2021-0725","DOIUrl":"https://doi.org/10.1515/jpem-2021-0725","url":null,"abstract":"Abstract Background Adrenal insufficiency (AI) is a life-threatening condition caused by an impaired secretion of the adrenal glucocorticoid and mineralocorticoid hormones. It comprises a heterogeneous group of primary, secondary and acquired disorders. Presentation differs according to the child’s age, but it usually presents with nonspecific and insidious symptoms and signs. The main purpose of this study was to describe and compare patients with primary or secondary AI. Methods Retrospective analysis of all patients with adrenal insufficiency followed at the Pediatric Endocrinology Unit in a tertiary care Portuguese hospital over the last 30 years. Data on family history, age at the first manifestation and at etiological diagnosis, and clinical presentation (symptoms, signs and laboratory evaluation) was gathered for all patients. Results Twenty-eight patients with AI were included; 67.9% were male, with a median (25th–75th percentile, P25–P75) age of 1 (0.5–36) month at the first presentation. The principal diagnostic categories were panhypopituitarism (42.9%) and congenital adrenal hyperplasia (25%). The most frequent manifestations (75%) were vomiting and weight loss. They were followed for a median (P25–P75) period of 3.5 (0.6–15.5) years. In respect to neurodevelopmental delay and learning difficulties, they were more common in the secondary AI group. Conclusions Despite medical advances, the diagnosis and management of AI remains a challenge, particularly in the pediatric population, and clinicians must have a high index of suspicion. An early identification of AI can prevent a potential lethal outcome, which may result from severe cardiovascular and hemodynamic instability.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"31 1","pages":"631 - 638"},"PeriodicalIF":0.0,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85651318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Kırmızıbekmez, Yasemin Kendir Demirkol, Özlem Akgün Doğan, Gülcan Seymen, Elif İnan Balcı, Pınar Atla, F. Dursun
Abstract Objectives Genetic factors have a key role in childhood obesity with higher rates in children than adults. Among the monogenic types of non-syndromic obesity, melanocortin-4 receptor (MC4R) deficiency is the most frequent cause. Beside pathogenic variants, single-nucleotide polymorphisms in MC4R gene are also associated with lower energy expenditure. The aim of this study was to estimate the frequency of MC4R variants and polymorphisms in a cohort of Turkish children and adolescents with severe early-onset obesity, and to understand the clinical features of patients. Methods Patients, 1–17 years of age, with the onset of obesity before 10 years of age and a body mass index (BMI) standard deviation score (SDS) of >2.3, and who had a family history of early-onset obesity in at least one of their first-degree relatives were included in the study. Beside routine blood tests genetic analyses for MC4R gene were performed. Results Analyses of MC4R revealed previously known variations in three (3.5%) patients, and pathogenic polymorphisms related with obesity in four (4.7%) patients. BMI SDS values were between 2.8 and 5.5 SDS in the pathogenic variant carrier group, and 2.8–4.9 SDS in the polymorphism group. Mean BMI SDS in variant-negative group was 3.4 ± 0.82. Conclusions Investigation of the MC4R in individuals with early-onset obesity and presence of obesity first-degree relatives is important. Hypertension is a rare comorbidity compared to other causes. Contrary to studies reporting that insulin resistance was absent or very rare, we found it as a frequent finding in both pathogenic variants and polymorphisms of MC4R.
{"title":"Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene","authors":"H. Kırmızıbekmez, Yasemin Kendir Demirkol, Özlem Akgün Doğan, Gülcan Seymen, Elif İnan Balcı, Pınar Atla, F. Dursun","doi":"10.1515/jpem-2021-0756","DOIUrl":"https://doi.org/10.1515/jpem-2021-0756","url":null,"abstract":"Abstract Objectives Genetic factors have a key role in childhood obesity with higher rates in children than adults. Among the monogenic types of non-syndromic obesity, melanocortin-4 receptor (MC4R) deficiency is the most frequent cause. Beside pathogenic variants, single-nucleotide polymorphisms in MC4R gene are also associated with lower energy expenditure. The aim of this study was to estimate the frequency of MC4R variants and polymorphisms in a cohort of Turkish children and adolescents with severe early-onset obesity, and to understand the clinical features of patients. Methods Patients, 1–17 years of age, with the onset of obesity before 10 years of age and a body mass index (BMI) standard deviation score (SDS) of >2.3, and who had a family history of early-onset obesity in at least one of their first-degree relatives were included in the study. Beside routine blood tests genetic analyses for MC4R gene were performed. Results Analyses of MC4R revealed previously known variations in three (3.5%) patients, and pathogenic polymorphisms related with obesity in four (4.7%) patients. BMI SDS values were between 2.8 and 5.5 SDS in the pathogenic variant carrier group, and 2.8–4.9 SDS in the polymorphism group. Mean BMI SDS in variant-negative group was 3.4 ± 0.82. Conclusions Investigation of the MC4R in individuals with early-onset obesity and presence of obesity first-degree relatives is important. Hypertension is a rare comorbidity compared to other causes. Contrary to studies reporting that insulin resistance was absent or very rare, we found it as a frequent finding in both pathogenic variants and polymorphisms of MC4R.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"1 1","pages":"657 - 662"},"PeriodicalIF":0.0,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72956265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caroline Wade, E. Burton, Leah I. Akinseye, Grace Nelson, Jamila Smith-young, Ahlee Kim
Abstract Objectives The prevalence of mental health issues has increased at an alarming rate during the COVID-19 pandemic. Furthermore, an exacerbated psychosocial burden in populations with chronic disease is observed. This cross-sectional study evaluated the psychosocial factors of pediatric type 1 diabetes (T1D) during the COVID-19 pandemic. Methods During April 2020, 15 min phone interviews were performed for pediatric T1D group (n=100) and healthy comparison group (n=93) to assess psychosocial functioning during the acute lockdown phase of the pandemic. The patient health questionnaire-4 was utilized to assess anxiety and depressive symptoms. An additional questionnaire to assess specific concerns related to T1D and COVID-19 was administered to the T1D group to explore potential causes for increased psychosocial burden. Results T1D was associated with a five-times higher risk of anxiety symptoms. Increased anxiety symptoms in T1D group appear to be, at least in part, due to fear of higher risk of severe COVID-19 infection and uncertainty regarding access to diabetes supplies. Conclusions This study provides a snapshot of mental well-being in a diverse population of patients with T1D in the acute phase of a crisis and underscores the need for timely, accurate medical information and distribution of medical resources for pediatric T1D population.
{"title":"Increased anxiety symptoms in pediatric type 1 diabetes during the acute phase of COVID-19 lockdown","authors":"Caroline Wade, E. Burton, Leah I. Akinseye, Grace Nelson, Jamila Smith-young, Ahlee Kim","doi":"10.1515/jpem-2022-0002","DOIUrl":"https://doi.org/10.1515/jpem-2022-0002","url":null,"abstract":"Abstract Objectives The prevalence of mental health issues has increased at an alarming rate during the COVID-19 pandemic. Furthermore, an exacerbated psychosocial burden in populations with chronic disease is observed. This cross-sectional study evaluated the psychosocial factors of pediatric type 1 diabetes (T1D) during the COVID-19 pandemic. Methods During April 2020, 15 min phone interviews were performed for pediatric T1D group (n=100) and healthy comparison group (n=93) to assess psychosocial functioning during the acute lockdown phase of the pandemic. The patient health questionnaire-4 was utilized to assess anxiety and depressive symptoms. An additional questionnaire to assess specific concerns related to T1D and COVID-19 was administered to the T1D group to explore potential causes for increased psychosocial burden. Results T1D was associated with a five-times higher risk of anxiety symptoms. Increased anxiety symptoms in T1D group appear to be, at least in part, due to fear of higher risk of severe COVID-19 infection and uncertainty regarding access to diabetes supplies. Conclusions This study provides a snapshot of mental well-being in a diverse population of patients with T1D in the acute phase of a crisis and underscores the need for timely, accurate medical information and distribution of medical resources for pediatric T1D population.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"16 1","pages":"627 - 630"},"PeriodicalIF":0.0,"publicationDate":"2022-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87630446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Karguppikar, C. Oza, Nikhil Shah, V. Khadilkar, K. Gondhalekar, A. Khadilkar
Abstract Objectives Children with type 1 diabetes (T1D) having diabetic nephropathy (DN) are at increased risk of developing end stage renal disease. The present study aimed to determine the prevalence of DN and its predictors in Indian children and youth with T1D. Methods This cross-sectional study included 319 children and youth (2.6–21 years) with T1D having disease duration of at least 2 years. Demographic data and laboratory findings were obtained using standard questionnaires and protocols. Diagnosis of diabetic nephropathy was based on albuminuria on two occasions within a period of 3 months. Results The prevalence of DN in our study subjects was 13.4%. 7.5% subjects were known cases of diabetic nephropathy on treatment with enalapril. Hypertension was found in 14.3% subjects with DN in contrast to 4.1% without DN (p<0.05). Duration of diabetes and estimated glucose disposal rate were the important predictors of DN. Interestingly, of the 43 children with DN, 11.3% (n=8) were under 10 years age. Conclusions We found a high prevalence of DN in children and youth with T1D including in children under the age of 10 years. Early screening and timely intervention are required to retard the disease progression and avoid end stage renal disease.
{"title":"Prevalence of nephropathy in Indian children and youth with type 1 diabetes mellitus","authors":"M. Karguppikar, C. Oza, Nikhil Shah, V. Khadilkar, K. Gondhalekar, A. Khadilkar","doi":"10.1515/jpem-2021-0644","DOIUrl":"https://doi.org/10.1515/jpem-2021-0644","url":null,"abstract":"Abstract Objectives Children with type 1 diabetes (T1D) having diabetic nephropathy (DN) are at increased risk of developing end stage renal disease. The present study aimed to determine the prevalence of DN and its predictors in Indian children and youth with T1D. Methods This cross-sectional study included 319 children and youth (2.6–21 years) with T1D having disease duration of at least 2 years. Demographic data and laboratory findings were obtained using standard questionnaires and protocols. Diagnosis of diabetic nephropathy was based on albuminuria on two occasions within a period of 3 months. Results The prevalence of DN in our study subjects was 13.4%. 7.5% subjects were known cases of diabetic nephropathy on treatment with enalapril. Hypertension was found in 14.3% subjects with DN in contrast to 4.1% without DN (p<0.05). Duration of diabetes and estimated glucose disposal rate were the important predictors of DN. Interestingly, of the 43 children with DN, 11.3% (n=8) were under 10 years age. Conclusions We found a high prevalence of DN in children and youth with T1D including in children under the age of 10 years. Early screening and timely intervention are required to retard the disease progression and avoid end stage renal disease.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"242 1","pages":"585 - 592"},"PeriodicalIF":0.0,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73637631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Guaragna, F. Ledesma, Victoria Zavanelli Manzano, A. Maciel-Guerra, G. Guerra‐Júnior, Marcelo Milone Silva, Pedro Luiz de Brito, M. Palandi de Mello
Abstract Objectives Wilm’s Tumor (WT) is the most common pediatric kidney cancer. Whereas most WTs are isolated, approximately 5% are associated with syndromes such as Denys-Drash (DDS), characterized by early onset nephropathy, disorders of sex development and predisposition to WT. Case presentation A 46,XY patient presenting with bilateral WT and genital ambiguity without nephropathy was heterozygous for the novel c.851_854dup variant in WT1 gene sequence. This variant affects the protein generating the frameshift p.(Ser285Argfs*14) that disrupts a nuclear localization signal (NLS) region. Conclusions This molecular finding is compatible with the severe scenario regarding the Wilm’s tumor presented by the patient even though nephropathy was absent.
{"title":"Bilateral Wilms’ tumor in a child with Denys-Drash syndrome: novel frameshift variant disrupts the WT1 nuclear location signaling region","authors":"M. Guaragna, F. Ledesma, Victoria Zavanelli Manzano, A. Maciel-Guerra, G. Guerra‐Júnior, Marcelo Milone Silva, Pedro Luiz de Brito, M. Palandi de Mello","doi":"10.1515/jpem-2021-0673","DOIUrl":"https://doi.org/10.1515/jpem-2021-0673","url":null,"abstract":"Abstract Objectives Wilm’s Tumor (WT) is the most common pediatric kidney cancer. Whereas most WTs are isolated, approximately 5% are associated with syndromes such as Denys-Drash (DDS), characterized by early onset nephropathy, disorders of sex development and predisposition to WT. Case presentation A 46,XY patient presenting with bilateral WT and genital ambiguity without nephropathy was heterozygous for the novel c.851_854dup variant in WT1 gene sequence. This variant affects the protein generating the frameshift p.(Ser285Argfs*14) that disrupts a nuclear localization signal (NLS) region. Conclusions This molecular finding is compatible with the severe scenario regarding the Wilm’s tumor presented by the patient even though nephropathy was absent.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"42 1","pages":"837 - 843"},"PeriodicalIF":0.0,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86609138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Erbas, Aygün Hajikhanova, Özge Besci, Kübra Yüksek Acinikli, K. Demir, E. Böber, A. Abacı
Abstract Objectives The exact mechanism of partial clinical remission in type 1 diabetes mellitus (T1DM) has not been elucidated yet. The severity of the inflammation at the time of diagnosis may affect the occurrence or duration of this phase. We aimed to investigate the relationship between hematological inflammatory parameters at the time of diagnosis in T1DM and (i) daily insulin requirement during the follow-up and (ii) the presence of partial clinical remission period, which was determined according to insulin dose-adjusted HbA1c levels. Methods A single-center retrospective study was conducted, including children who were diagnosed with T1DM, were positive for at least one autoantibody, and were followed up for one year in our clinic between 2010 and 2020. Results Sixty-eight patients (55.9% female, 64.7% prepubertal) were included in the study, whose mean age was 8.4 ± 4.2 years. A total of 38 patients (55.9%) had partial clinical remission. None of the initial hematological indices were associated with the occurrence of partial remission. Initial neutrophil/lymphocyte ratio (NLR) and derived-NLR (d-NLR) levels were significantly lower (p=0.011 and 0.033, respectively) and lymphocyte/monocyte ratio (LMR) levels were significantly higher (p=0.005) in patients who showed an insulin requirement of <0.5 IU/kg/day at the 3rd month after diagnosis. Conclusions Initial hematological parameters were not found as a predictor of partial clinical remission period in T1DM in children. However, a lower NLR and d-NLR, or a higher LMR at the time of diagnosis can be used as an indicator of a low daily insulin need at the 3rd month of T1DM.
{"title":"Initial neutrophil/lymphocyte and lymphocyte/monocyte ratios can predict future insulin need in newly diagnosed type 1 diabetes mellitus","authors":"I. Erbas, Aygün Hajikhanova, Özge Besci, Kübra Yüksek Acinikli, K. Demir, E. Böber, A. Abacı","doi":"10.1515/jpem-2021-0564","DOIUrl":"https://doi.org/10.1515/jpem-2021-0564","url":null,"abstract":"Abstract Objectives The exact mechanism of partial clinical remission in type 1 diabetes mellitus (T1DM) has not been elucidated yet. The severity of the inflammation at the time of diagnosis may affect the occurrence or duration of this phase. We aimed to investigate the relationship between hematological inflammatory parameters at the time of diagnosis in T1DM and (i) daily insulin requirement during the follow-up and (ii) the presence of partial clinical remission period, which was determined according to insulin dose-adjusted HbA1c levels. Methods A single-center retrospective study was conducted, including children who were diagnosed with T1DM, were positive for at least one autoantibody, and were followed up for one year in our clinic between 2010 and 2020. Results Sixty-eight patients (55.9% female, 64.7% prepubertal) were included in the study, whose mean age was 8.4 ± 4.2 years. A total of 38 patients (55.9%) had partial clinical remission. None of the initial hematological indices were associated with the occurrence of partial remission. Initial neutrophil/lymphocyte ratio (NLR) and derived-NLR (d-NLR) levels were significantly lower (p=0.011 and 0.033, respectively) and lymphocyte/monocyte ratio (LMR) levels were significantly higher (p=0.005) in patients who showed an insulin requirement of <0.5 IU/kg/day at the 3rd month after diagnosis. Conclusions Initial hematological parameters were not found as a predictor of partial clinical remission period in T1DM in children. However, a lower NLR and d-NLR, or a higher LMR at the time of diagnosis can be used as an indicator of a low daily insulin need at the 3rd month of T1DM.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"30 1 1","pages":"593 - 602"},"PeriodicalIF":0.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80476159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emre Sarıkaya, Fırat Özçelik, Ülkü Gül Siraz, N. Hatipoğlu, T. Güneş, M. Dündar
Abstract Objectives Arthrogryposis multiplex congenita-5 (AMC5) is an autosomal recessive disease caused by homozygous or compound heterozygous mutations in the TOR1A gene on chromosome 9q34. Congenital multiple joint contractures with microcephaly, typical facial dysmorphism, developmental delay, strabismus, tremor, and increased tone are the main characteristics defined in seven patients thus far. One third of the individuals with monoallelic mutations of the gene develop isolated early-onset dystonia (DYT1 dystonia), which is inherited in an autosomal dominant fashion, with variable expressivity and incomplete penetrance. We believe that different inheritance patterns of the same gene resulting in different phenotypes will provide an opportunity to understand other similar disease groups and different aspects of gene functions. Case presentation We present a case with severe arthrogryposis multiplex congenita, respiratory failure, and feeding difficulties, with additional hitherto unreported symptoms, such as spontaneous bone fracture, sliding esophageal hernia, and uterine prolapse. The patient carried a novel homozygous variant (c.835delA, p.Lys275Asnfs*3) in the TOR1A gene (NM_000113.2). Conclusions We want to contribute to the phenotypic and genotypic spectra of this extremely rare disease.
{"title":"A very rare cause of arthrogryposis multiplex congenita: a novel mutation in TOR1A","authors":"Emre Sarıkaya, Fırat Özçelik, Ülkü Gül Siraz, N. Hatipoğlu, T. Güneş, M. Dündar","doi":"10.1515/jpem-2021-0766","DOIUrl":"https://doi.org/10.1515/jpem-2021-0766","url":null,"abstract":"Abstract Objectives Arthrogryposis multiplex congenita-5 (AMC5) is an autosomal recessive disease caused by homozygous or compound heterozygous mutations in the TOR1A gene on chromosome 9q34. Congenital multiple joint contractures with microcephaly, typical facial dysmorphism, developmental delay, strabismus, tremor, and increased tone are the main characteristics defined in seven patients thus far. One third of the individuals with monoallelic mutations of the gene develop isolated early-onset dystonia (DYT1 dystonia), which is inherited in an autosomal dominant fashion, with variable expressivity and incomplete penetrance. We believe that different inheritance patterns of the same gene resulting in different phenotypes will provide an opportunity to understand other similar disease groups and different aspects of gene functions. Case presentation We present a case with severe arthrogryposis multiplex congenita, respiratory failure, and feeding difficulties, with additional hitherto unreported symptoms, such as spontaneous bone fracture, sliding esophageal hernia, and uterine prolapse. The patient carried a novel homozygous variant (c.835delA, p.Lys275Asnfs*3) in the TOR1A gene (NM_000113.2). Conclusions We want to contribute to the phenotypic and genotypic spectra of this extremely rare disease.","PeriodicalId":16746,"journal":{"name":"Journal of Pediatric Endocrinology and Metabolism","volume":"7 1","pages":"845 - 850"},"PeriodicalIF":0.0,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79556169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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