Abstract. Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disease that is characterized by loss of subcutaneous and visceral adipose tissues, and associated with dysregulation of glycolipid metabolism. In the present study, we reported the clinical manifestations and treatments of Japanese siblings with CGL caused by BSCL2 gene mutations with a clinical course of approximately 20 yr. Comprehensive management with metreleptin therapy, dietary control with additional medication, and psychosocial counseling in line with the patients’ stages of growth and development were important in achieving long-term metabolic control of this condition.
{"title":"The long-term management of congenital generalized lipodystrophy (Berardinelli-Seip syndrome): the clinical manifestations of Japanese siblings for approximately 20 years","authors":"Miwako Maeda, T. Maeda, Ken Ebihara, K. Ihara","doi":"10.1297/cpe.28.139","DOIUrl":"https://doi.org/10.1297/cpe.28.139","url":null,"abstract":"Abstract. Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disease that is characterized by loss of subcutaneous and visceral adipose tissues, and associated with dysregulation of glycolipid metabolism. In the present study, we reported the clinical manifestations and treatments of Japanese siblings with CGL caused by BSCL2 gene mutations with a clinical course of approximately 20 yr. Comprehensive management with metreleptin therapy, dietary control with additional medication, and psychosocial counseling in line with the patients’ stages of growth and development were important in achieving long-term metabolic control of this condition.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"139 - 145"},"PeriodicalIF":1.4,"publicationDate":"2019-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48657549","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}
Kosei Hasegawa, Hiromi Ihoriya, Natsuko Futagawa, Y. Higuchi, Hiroki Tsuchiya, Takashi Shibata, Yumiko Hayashi, Katsuhiro Kobayashi, H. Tsukahara
Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused by genetic mutations in AVPR2 or AQP2 (1). AVPR2 is located at the Xq28 locus, and it encodes arginine vasopressin receptor 2 (AVPR2). Mutations in AVPR2 have been associated with X-linked NDI. AQP2 is located at the 12q13.12 locus, and it encodes the water transporter aquaporin-2. Mutations in AQP2 result in autosomal NDI. Here, we describe a male infant with a novel AVPR2 variant who was referred to our hospital due to delayed head control.
{"title":"Novel AVPR2 variant in a male infant with nephrogenic diabetes insipidus who showed delayed head control","authors":"Kosei Hasegawa, Hiromi Ihoriya, Natsuko Futagawa, Y. Higuchi, Hiroki Tsuchiya, Takashi Shibata, Yumiko Hayashi, Katsuhiro Kobayashi, H. Tsukahara","doi":"10.1297/cpe.28.155","DOIUrl":"https://doi.org/10.1297/cpe.28.155","url":null,"abstract":"Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused by genetic mutations in AVPR2 or AQP2 (1). AVPR2 is located at the Xq28 locus, and it encodes arginine vasopressin receptor 2 (AVPR2). Mutations in AVPR2 have been associated with X-linked NDI. AQP2 is located at the 12q13.12 locus, and it encodes the water transporter aquaporin-2. Mutations in AQP2 result in autosomal NDI. Here, we describe a male infant with a novel AVPR2 variant who was referred to our hospital due to delayed head control.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"155 - 158"},"PeriodicalIF":1.4,"publicationDate":"2019-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46023877","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}
K. Yoshizaki, R. Hachiya, Yutaro Tomobe, Uiko Kaku, K. Akiba, H. Shima, S. Narumi, Y. Hasegawa
Abstract. Aspiration pneumonia is a common complication of myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy (MIRAGE) syndrome. However, the detailed clinical course of aspiration pneumonia in neonates and infants diagnosed with this disorder remains unclear. We report a case of a 2-yr-old girl diagnosed with MIRAGE syndrome during the early neonatal period. The patient developed 3 episodes of aspiration pneumonia until 4 mo of age, and this complication was attributed to esophageal hypoperistalsis secondary to achalasia and gastroesophageal reflux. Enteral feeding via a duodenal tube effectively prevented further episodes of aspiration pneumonia in this patient.
{"title":"MIRAGE syndrome with recurrent pneumonia probably associated with gastroesophageal reflux and achalasia: A case report","authors":"K. Yoshizaki, R. Hachiya, Yutaro Tomobe, Uiko Kaku, K. Akiba, H. Shima, S. Narumi, Y. Hasegawa","doi":"10.1297/cpe.28.147","DOIUrl":"https://doi.org/10.1297/cpe.28.147","url":null,"abstract":"Abstract. Aspiration pneumonia is a common complication of myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy (MIRAGE) syndrome. However, the detailed clinical course of aspiration pneumonia in neonates and infants diagnosed with this disorder remains unclear. We report a case of a 2-yr-old girl diagnosed with MIRAGE syndrome during the early neonatal period. The patient developed 3 episodes of aspiration pneumonia until 4 mo of age, and this complication was attributed to esophageal hypoperistalsis secondary to achalasia and gastroesophageal reflux. Enteral feeding via a duodenal tube effectively prevented further episodes of aspiration pneumonia in this patient.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"147 - 153"},"PeriodicalIF":1.4,"publicationDate":"2019-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48849207","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}
Abstract. Significant differences in levothyroxine (LT4) dosages for congenital hypothyroidism (CH), which can be permanent (P-CH) or transient (T-CH), and their respective cutoff values have been reported. In Japanese children, however, these values are unknown, and were thus determined in this retrospective single-center study, which included 34 patients— 19 with P-CH and 15 with T-CH. The LT4 dosages of the two groups at ages 1 and 3 yr were compared, and receiver operating characteristic (ROC) analysis was performed to identify the cutoff dosages. The results showed that the LT4 dosages of the P-CH and T-CH groups differed significantly at both ages. When LT4 dosage cutoff at 1 yr of age was set at 2.4 μg/kg/d, the sensitivity and specificity were 93% and 74%, respectively, and when it was set at 1.3 μg/kg/d at 3 yr of age, they were 80% and 84%, respectively, suggesting that when LT4 dosages are ≤2.4 μg/kg/d at 1 yr and ≤1.3 μg/kg/d at 3 yr of age, T-CH should be suspected.
{"title":"Levothyroxine dosages less than 2.4 μg/kg/day at 1 year and 1.3 μg/kg/day at 3 years of age may predict transient congenital hypothyroidism","authors":"S. Higuchi, Y. Hasegawa","doi":"10.1297/cpe.28.127","DOIUrl":"https://doi.org/10.1297/cpe.28.127","url":null,"abstract":"Abstract. Significant differences in levothyroxine (LT4) dosages for congenital hypothyroidism (CH), which can be permanent (P-CH) or transient (T-CH), and their respective cutoff values have been reported. In Japanese children, however, these values are unknown, and were thus determined in this retrospective single-center study, which included 34 patients— 19 with P-CH and 15 with T-CH. The LT4 dosages of the two groups at ages 1 and 3 yr were compared, and receiver operating characteristic (ROC) analysis was performed to identify the cutoff dosages. The results showed that the LT4 dosages of the P-CH and T-CH groups differed significantly at both ages. When LT4 dosage cutoff at 1 yr of age was set at 2.4 μg/kg/d, the sensitivity and specificity were 93% and 74%, respectively, and when it was set at 1.3 μg/kg/d at 3 yr of age, they were 80% and 84%, respectively, suggesting that when LT4 dosages are ≤2.4 μg/kg/d at 1 yr and ≤1.3 μg/kg/d at 3 yr of age, T-CH should be suspected.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"127 - 133"},"PeriodicalIF":1.4,"publicationDate":"2019-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43242341","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}
Tsuyoshi Nishibukuro, Junko Igaki-Miyamoto, Y. Hasegawa
Abstract. Disorders of sex development (DSD) are a group of congenital conditions presenting with differences in the chromosomal, gonadal, or anatomic sex development. Evaluating the chromosomes, gonads, and internal and external genitalia of the patients is important for understanding DSD. Furthermore, confirming the presence of a uterus is essential for the assessment of the internal genitalia status. Although the uterus can be identified by ultrasonography, magnetic resonance imaging, or laparoscopy, it may be easily overlooked. Here, we report the case of a patient with mixed gonadal dysgenesis, in whom the presence of a uterus could not be confirmed before the initiation of estrogen replacement therapy despite the performance of various tests. The detection of the uterus was prompted by an atypical genital bleeding. This case implies that physicians may have difficulties identifying the uterus in female patients with DSD before the initiation of estrogen treatment.
{"title":"Uterus in mixed gonadal dysgenesis was detected by continuous irregular vaginal bleeding","authors":"Tsuyoshi Nishibukuro, Junko Igaki-Miyamoto, Y. Hasegawa","doi":"10.1297/cpe.28.135","DOIUrl":"https://doi.org/10.1297/cpe.28.135","url":null,"abstract":"Abstract. Disorders of sex development (DSD) are a group of congenital conditions presenting with differences in the chromosomal, gonadal, or anatomic sex development. Evaluating the chromosomes, gonads, and internal and external genitalia of the patients is important for understanding DSD. Furthermore, confirming the presence of a uterus is essential for the assessment of the internal genitalia status. Although the uterus can be identified by ultrasonography, magnetic resonance imaging, or laparoscopy, it may be easily overlooked. Here, we report the case of a patient with mixed gonadal dysgenesis, in whom the presence of a uterus could not be confirmed before the initiation of estrogen replacement therapy despite the performance of various tests. The detection of the uterus was prompted by an atypical genital bleeding. This case implies that physicians may have difficulties identifying the uterus in female patients with DSD before the initiation of estrogen treatment.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"135 - 138"},"PeriodicalIF":1.4,"publicationDate":"2019-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45385502","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}
Tomohiro Hori, H. Ohnishi, Tomonori Kadowaki, N. Kawamoto, H. Matsumoto, O. Ohara, T. Fukao
Abstract. Hashimoto’s thyroiditis (HT) is an autoimmune disease thought to involve a combination of genetic and environmental factors, but its detailed pathogenesis is unknown. We present a family with haploinsufficiency of the gene encoding tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) and show a link with HT in a three-generation pedigree. Currently, TNFAIP3 polymorphisms are associated with several autoimmune diseases, and haploinsufficiency of A20 was recently observed in families with an early-onset autoinflammatory disease resembling Behçet’s disease. However, HT has not been linked with TNFAIP3 variants. We analyzed TNFAIP3 and human leukocyte antigen (HLA) in the family showing HT as an autosomal dominant trait, and identified a novel heterozygous c.2209delC mutation of TNFAIP3 in the members with HT. The known HLA haplotypes linked to HT could not be identified. Based on our analysis of this pedigree, we consider HT as a possible phenotype of A20 haploinsufficiency.
{"title":"Autosomal dominant Hashimoto’s thyroiditis with a mutation in TNFAIP3","authors":"Tomohiro Hori, H. Ohnishi, Tomonori Kadowaki, N. Kawamoto, H. Matsumoto, O. Ohara, T. Fukao","doi":"10.1297/cpe.28.91","DOIUrl":"https://doi.org/10.1297/cpe.28.91","url":null,"abstract":"Abstract. Hashimoto’s thyroiditis (HT) is an autoimmune disease thought to involve a combination of genetic and environmental factors, but its detailed pathogenesis is unknown. We present a family with haploinsufficiency of the gene encoding tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) and show a link with HT in a three-generation pedigree. Currently, TNFAIP3 polymorphisms are associated with several autoimmune diseases, and haploinsufficiency of A20 was recently observed in families with an early-onset autoinflammatory disease resembling Behçet’s disease. However, HT has not been linked with TNFAIP3 variants. We analyzed TNFAIP3 and human leukocyte antigen (HLA) in the family showing HT as an autosomal dominant trait, and identified a novel heterozygous c.2209delC mutation of TNFAIP3 in the members with HT. The known HLA haplotypes linked to HT could not be identified. Based on our analysis of this pedigree, we consider HT as a possible phenotype of A20 haploinsufficiency.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"91 - 96"},"PeriodicalIF":1.4,"publicationDate":"2019-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.91","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45393064","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}
Abstract. In recent years, immune checkpoint inhibitor therapy has attracted a great deal of attention in the field of cancer treatment. In the clinical setting, antibodies targeting programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have been successfully used to treat adult patients with various types of intractable cancer. However, in a substantial number of patients, ICI therapy is associated with autoimmune toxicities known as immune-related adverse events (IRAEs). Endocrinopathies, such as hypophysitis or autoimmune thyroid disease, may occur and can present unique clinical features that have not been documented with traditional chemotherapies. A Japanese clinical trial evaluating the anti-PD-1 antibody nivolumab for the treatment of pediatric patients with refractory malignant solid tumors and Hodgkin lymphoma has been ongoing since 2017. Moreover, tumors associated with Lynch syndrome, a hereditary form of mismatch repair deficiency, are being focused and represent the next target for ICI therapy in Japan. For the safe management of pediatric cancer patients treated with ICIs, pediatric endocrinologists must be aware of the risk of autoimmune endocrinopathies and perform relevant screening tests at appropriate stages of growth and development.
{"title":"Immune checkpoint inhibitor therapy for pediatric cancers: A mini review of endocrine adverse events","authors":"K. Ihara","doi":"10.1297/cpe.28.59","DOIUrl":"https://doi.org/10.1297/cpe.28.59","url":null,"abstract":"Abstract. In recent years, immune checkpoint inhibitor therapy has attracted a great deal of attention in the field of cancer treatment. In the clinical setting, antibodies targeting programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have been successfully used to treat adult patients with various types of intractable cancer. However, in a substantial number of patients, ICI therapy is associated with autoimmune toxicities known as immune-related adverse events (IRAEs). Endocrinopathies, such as hypophysitis or autoimmune thyroid disease, may occur and can present unique clinical features that have not been documented with traditional chemotherapies. A Japanese clinical trial evaluating the anti-PD-1 antibody nivolumab for the treatment of pediatric patients with refractory malignant solid tumors and Hodgkin lymphoma has been ongoing since 2017. Moreover, tumors associated with Lynch syndrome, a hereditary form of mismatch repair deficiency, are being focused and represent the next target for ICI therapy in Japan. For the safe management of pediatric cancer patients treated with ICIs, pediatric endocrinologists must be aware of the risk of autoimmune endocrinopathies and perform relevant screening tests at appropriate stages of growth and development.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"59 - 68"},"PeriodicalIF":1.4,"publicationDate":"2019-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.59","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43622516","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}
Y. Saijo, Y. Ito, E. Yoshioka, Yukihiro Sato, Machiko Minatoya, A. Araki, C. Miyashita, R. Kishi
Abstract. This study aimed to construct a childhood obesity risk index based on predictors identified in pregnant women and 1-yr-old infants. The primary outcome was an identified obesity index of > 20% at 6–8 yr of age. Of a total sample size of 6,846 mother-child pairs, 80% and 20% were randomly allocated to the derivation and validation cohorts, respectively. For the derivation cohort, univariate and multivariate logistic regression analyses of data were conducted to identify the final predictors to determine the childhood obesity risk score algorithm. These included pre-pregnancy body mass index (BMI), child’s gender, smoking during pregnancy, education, and obesity index at one yr of age. The β coefficients for categories of predictor variables were each divided by the smallest value among them. The quotient was rounded off to the integer and assigned to the risk score, and a value of zero was assigned to reference categories. A total risk score was calculated for each individual. A cutoff point ≥ 16 had 22.2% and 21.8% positive predictive values in the derivation and validation cohorts, respectively. In conclusion, the childhood obesity risk score algorithm was constructed based on generic predictors that can be easily obtained from maternal and child health handbooks.
{"title":"Identifying a risk score for childhood obesity based on predictors identified in pregnant women and 1-year-old infants: An analysis of the data of the Hokkaido Study on Environment and Children’s Health","authors":"Y. Saijo, Y. Ito, E. Yoshioka, Yukihiro Sato, Machiko Minatoya, A. Araki, C. Miyashita, R. Kishi","doi":"10.1297/cpe.28.81","DOIUrl":"https://doi.org/10.1297/cpe.28.81","url":null,"abstract":"Abstract. This study aimed to construct a childhood obesity risk index based on predictors identified in pregnant women and 1-yr-old infants. The primary outcome was an identified obesity index of > 20% at 6–8 yr of age. Of a total sample size of 6,846 mother-child pairs, 80% and 20% were randomly allocated to the derivation and validation cohorts, respectively. For the derivation cohort, univariate and multivariate logistic regression analyses of data were conducted to identify the final predictors to determine the childhood obesity risk score algorithm. These included pre-pregnancy body mass index (BMI), child’s gender, smoking during pregnancy, education, and obesity index at one yr of age. The β coefficients for categories of predictor variables were each divided by the smallest value among them. The quotient was rounded off to the integer and assigned to the risk score, and a value of zero was assigned to reference categories. A total risk score was calculated for each individual. A cutoff point ≥ 16 had 22.2% and 21.8% positive predictive values in the derivation and validation cohorts, respectively. In conclusion, the childhood obesity risk score algorithm was constructed based on generic predictors that can be easily obtained from maternal and child health handbooks.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"81 - 89"},"PeriodicalIF":1.4,"publicationDate":"2019-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.81","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42540769","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}
T. Tajima, A. Nakamura, Makiko Oguma, Masayo Yamazaki
Abstract. Congenital central hypothyroidism (C-CH) is caused by defects in the secretion of thyrotropin-releasing hormone (TRH) and/or TSH, leading to an impairment in the release of hormones from the thyroid. The causes of C-CH include congenital anomalies of the hypothalamic-pituitary regions and several genetic defects. In terms of endocrinology, C-CH is divided into two categories: (1) accompanied by another pituitary hormone deficiency and called combined pituitary hormone deficiency, and (2) isolated C-CH, showing mainly TSH deficiency. For isolated C-CH, a mutation in the TSH gene (TSHB) encoding the β-subunit of the protein was first found in 1990 by Japanese researchers, and thereafter several mutations in TSHB have been reported. Mutations in the thyrotropin-releasing hormone receptor gene (TRHR), as well as genetic defects in immunoglobulin superfamily 1 (IGSF1), have also been identified. It was recently found that isolated C-CH is caused by mutations in transducin β-like 1 X-linked and insulin receptor substrate 4. It is noted that all patients with TSHB deficiency and some with IGSF1 deficiency show severe hypothyroidism soon after birth. Among the causes of C-CH, high frequency of mutations in IGSF1 is the most prevalent. This review focuses on recent findings on isolated C-CH.
{"title":"Recent advances in research on isolated congenital central hypothyroidism","authors":"T. Tajima, A. Nakamura, Makiko Oguma, Masayo Yamazaki","doi":"10.1297/cpe.28.69","DOIUrl":"https://doi.org/10.1297/cpe.28.69","url":null,"abstract":"Abstract. Congenital central hypothyroidism (C-CH) is caused by defects in the secretion of thyrotropin-releasing hormone (TRH) and/or TSH, leading to an impairment in the release of hormones from the thyroid. The causes of C-CH include congenital anomalies of the hypothalamic-pituitary regions and several genetic defects. In terms of endocrinology, C-CH is divided into two categories: (1) accompanied by another pituitary hormone deficiency and called combined pituitary hormone deficiency, and (2) isolated C-CH, showing mainly TSH deficiency. For isolated C-CH, a mutation in the TSH gene (TSHB) encoding the β-subunit of the protein was first found in 1990 by Japanese researchers, and thereafter several mutations in TSHB have been reported. Mutations in the thyrotropin-releasing hormone receptor gene (TRHR), as well as genetic defects in immunoglobulin superfamily 1 (IGSF1), have also been identified. It was recently found that isolated C-CH is caused by mutations in transducin β-like 1 X-linked and insulin receptor substrate 4. It is noted that all patients with TSHB deficiency and some with IGSF1 deficiency show severe hypothyroidism soon after birth. Among the causes of C-CH, high frequency of mutations in IGSF1 is the most prevalent. This review focuses on recent findings on isolated C-CH.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"69 - 79"},"PeriodicalIF":1.4,"publicationDate":"2019-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.69","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47047390","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}
Abstract. Type 1 diabetes (T1D) is a chronic T-cell mediated autoimmune disease characterized by destruction of beta cells. Although new data have better defined the complex etiology underling the interrelation of genetic and environmental factors in the natural history of T1D, relevant pieces of the puzzle still are missing. Genetic predisposition is mainly associated to some histocompatibility leukocyte antigen (HLA) alleles; however, recent data suggest that new as well as still unknown genes might better define the complex multigenetic risk of the disease. In addition to the genetic effects, the concordance in familial aggregation in T1D indicates a pivotal role of environmental factors in the course of the disease, facilitating autoantibodies production. JDRF has recently proposed a new early stage of T1D according to which the detection of two or more autoantibodies in the blood, might describe those children at increased risk of developing T1D during the following years. In contrast to the improvements reached by prediction models, to date primary, secondary and tertiary prevention have still failed to achieve a safe and efficacious intervention strategies. Anyway, the most recent progresses in this field pave the way for future studies, with the aim of preventing T1D in children.
{"title":"Prediction and prevention of type 1 diabetes in children","authors":"F. Chiarelli, C. Giannini, M. Primavera","doi":"10.1297/cpe.28.43","DOIUrl":"https://doi.org/10.1297/cpe.28.43","url":null,"abstract":"Abstract. Type 1 diabetes (T1D) is a chronic T-cell mediated autoimmune disease characterized by destruction of beta cells. Although new data have better defined the complex etiology underling the interrelation of genetic and environmental factors in the natural history of T1D, relevant pieces of the puzzle still are missing. Genetic predisposition is mainly associated to some histocompatibility leukocyte antigen (HLA) alleles; however, recent data suggest that new as well as still unknown genes might better define the complex multigenetic risk of the disease. In addition to the genetic effects, the concordance in familial aggregation in T1D indicates a pivotal role of environmental factors in the course of the disease, facilitating autoantibodies production. JDRF has recently proposed a new early stage of T1D according to which the detection of two or more autoantibodies in the blood, might describe those children at increased risk of developing T1D during the following years. In contrast to the improvements reached by prediction models, to date primary, secondary and tertiary prevention have still failed to achieve a safe and efficacious intervention strategies. Anyway, the most recent progresses in this field pave the way for future studies, with the aim of preventing T1D in children.","PeriodicalId":10678,"journal":{"name":"Clinical Pediatric Endocrinology","volume":"28 1","pages":"43 - 57"},"PeriodicalIF":1.4,"publicationDate":"2019-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1297/cpe.28.43","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44869569","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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