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The cardinal phenotypic hallmarks of Marfan syndrome (MFS) include cardiac, ocular, and skeletal abnormalities. Since the clinical phenotype of MFS is highly heterogeneous, with certain symptoms appearing as children age, the diagnostic process and establishing a genotype-phenotype association in childhood MFS can be challenging. The lack of sufficient childhood studies also makes it difficult to interpret the subject. This study aims to evaluate the relationship between clinical symptoms used as diagnostic criteria and FBN1 variations in children with MFS. This study investigated the relationships between genotypes and phenotypes in 131 children suspected of having Marfan syndrome (MFS). Diagnosis of MFS was made according to the revised Ghent nosology. FBN1 variants were categorized based on exon regions, type of variant, and pathogenicity classes. These FBN1 variants were then correlated with the clinical manifestations including cardiovascular, ocular, facial, and skeletal abnormalities. Out of the children, 43 were diagnosed with MFS. FBN1 variant was identified in 32 (74.4%) of the MFS children. MFS diagnosis could not be made in five (15.6%) FBN1 variant-positive children. The most common cardinal finding is cardiac anomalies n = 38 (88.3%). The most common FBN1 pathogenic variant was c.1786 T > C/p.Cys596Arg n = 4 (12.5%). The distribution of pathogenic variants was as follows: 29 (90.6%) missense, 2 (6.3%) frameshift, and 1 (3.1%) nonsense. The numbers of AD and EL of the variant-positive children were 16 (50%) and 14 (43.7%), respectively. Ocular abnormalities were more common in children with FBN1-positive MFS (p = 0.009). There was no difference in the number of cardiac abnormalities between FBN1-positive and FBN1-negative MFS patients (p = 0.139). Conclusion: This study examines the relationship between FBN1 variants and clinical features used as diagnostic criteria in MFS children. The findings emphasize the importance of long-term monitoring of heterogeneous clinical phenotypes and bioinformatic reanalysis in determining the genotype-phenotype relationship in children, as MFS symptoms can vary with age. What is Known: ⢠Marfan syndrome has highly variable phenotypic heterogeneity. ⢠The genotype-phenotype relationship in childhood Marfan syndrome is not clear enough due to the variation in the time of onset of the findings. What is New: ⢠This article provides regional data for the field of research on genotype-phenotype relationships in childhood Marfan syndrome. ⢠Long-term follow-up of clinical findings and bioinformatics reanalysis is an important requirement for a well-established genotype-phenotype relationship in childhood Marfan syndrome.
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Fibrilina-1 , Genótipo , Síndrome de Marfan , Fenótipo , Humanos , Síndrome de Marfan/genética , Síndrome de Marfan/diagnóstico , Criança , Feminino , Masculino , Fibrilina-1/genética , Pré-Escolar , Adolescente , Turquia/epidemiologia , Lactente , Estudos de Associação Genética , Mutação , AdipocinasRESUMO
OBJECTIVE: Bioinactive growth hormone (BGH) is a structurally abnormal, biologically inactive, but immunoreactive form of growth hormone encoded by pathogenic growth hormone 1 gene variants. The underlying cause of the defective physiology is decreased BGH binding affinity to both growth hormone binding proteins and growth hormone receptors (GHRs). GHR cannot dimerize when it is in a quiescent state because BGH cannot activate it. Nondimerized GHR is unable to activate intracytoplasmic signaling pathway molecules such as Janus kinase 2 and signal transducer and activator of transcription, which initiate insulin-like growth factor-1 (IGF-1) transcription. IGF-1 cannot therefore be synthesized and IGF-1 levels in the circulation decrease. In contrast to children with growth hormone insensitivity, children with short stature due to BGH, known as Kowarski syndrome, exhibit an outstanding linear growth response to recombinant growth hormone therapy. For a number of reasons, differential diagnosis presents some difficulties. Similar diseases caused by genetic abnormalities that cause short stature range in severity from minor to severe clinical spectrum. Furthermore, some patients with Kowarski syndrome have previously been diagnosed with familial short stature, constitutional delayed puberty, and idiopathic short stature. This paper aims to review the particular clinical and laboratory findings of BGH. METHODS: This study collected clinical and laboratory data from KS cases reported in the literature. RESULTS: This review reports that KS cases have lower SDSs for height and IGF-1 compared to growth hormone deficiency. CONCLUSION: The diversity of genetic defects underlying Kowarski syndrome (KS) will provide new insights into growth hormone insensitivity. As the availability of genetic analysis, including functional investigations expands, researchers will identify new underlying genetic pathways.
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Nanismo Hipofisário , Hormônio do Crescimento Humano , Criança , Humanos , Hormônio do Crescimento , Fator de Crescimento Insulin-Like I/análise , Nanismo Hipofisário/tratamento farmacológico , Nanismo Hipofisário/genética , Hormônio do Crescimento Humano/uso terapêuticoRESUMO
BACKGROUND/OBJECTIVE: Although the physiology of minipuberty is well established, it is not fully explained why it occurs. It has been suggested that minipuberty contributes to the development of reproductive organs, somatic growth, cognitive/behavioural and sex-specific brain development. Given the well-known trade-off between the reproductive/endocrine and immune systems in adults, the immunological approach to minipuberty, which is characterized by transient activation of the hypothalamo-pituitary gonadal (HPG) axis, seems to be ignored. This study focused on the relationship of the lymphocyte subsets with gonadotrophin and sex hormones during the minipuberty. MATERIALS AND METHODS: A total of 121 newborns (58 male) were included in this cross-sectional study. The hormone and lymphocyte subsets studied were as follow: follicle-stimulating hormone (FSH), luteinizing hormone (LH) estradiol (E), testosterone (T), CD19, CD16/56, CD3, CD3/CD4, CD3/CD8 and HLA-DR as lymphocyte activation marker. RESULTS: The mean FSH levels were higher in females (15.15 ± 10.12 mIU/ml vs, 2.61 ± 1.74 mIU/ml) and LH in males (5.80 ± 2.51 mIU/ml vs. 1.91 ± 12.89 mIU/ml) (P < .001 for each). The mean percentages of the CD3/CD4 levels were higher in females (54.61 ± 6.70% vs. 51.17 ± 6.77%) and CD3/CD8 in males (21.49 ± 4.82% vs. 17.31 ± 3.66%) (P < .001 for each). In the females, the mean FSH levels negatively correlated with CD3/CD4 (rFSH-CD3/CD4 = -0.423, P = .001) and positively correlated with CD3/CD8 (rFSH-CD3/CD8 = 0.311, P = .013). In the males, LH positively correlated with CD3/CD4 (rLH-CD3/CD4 = 0.406, P < .001) and negatively correlated with CD3/CD8 (rLH-CD3/CD8 = -0.486, P < .001). CONCLUSION: This study showed that the mean CD3/CD4 levels were higher in female and CD3/CD8 in male newborns, indicating that there was a sexual dimorphism in favour of immunostimulant in females and immunosuppressor components of immune response in males during the minipuberty. These interactions point to sex-specific trade-off between reproductive/endocrine and immune systems, which it reflects the an investment favouring in the reproductive system against the immune response during minipuberty, which is critical period for adult fertility, especially in males.
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Imunidade , Subpopulações de Linfócitos , Caracteres Sexuais , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Hormônio Luteinizante , MasculinoRESUMO
BACKGROUND/AIM: Biotin is a vital micronutrient that plays a role in metabolic homeostasis and the regulation of innate and adaptive immune system functions. Biotinidase deficiency (BTD) leads to impairment in biotin-dependent immune functions. This study focused on immunophenotypic analysis of lymphocyte subsets in newborns with BTD. PATIENTS AND METHODS: A total of 181 (95 female and 86 male; 114 had BTD and 67 were healthy) newborns underwent biotinidase enzyme activity, molecular and lymphocyte immunophenotyping analyses. BTD is classified into four biochemical phenotypes: profound, partial, heterozygous and normal. The following lymphocyte subsets were studied in all participants: total B lymphocyte (CD19), total T lymphocyte (CD3), helper T lymphocyte (CD3/CD4), cytotoxic T lymphocyte (CTL) (CD3/CD8), natural killer T lymphocyte (CD16/56) and a T-lymphocyte activation marker (HLA-DR). RESULTS: The percentages of lymphocyte subsets were similar in newborns with and without BTD. In all newborns with BTD, the mean CD3/CD4 levels were higher in females, while the CD3/CD8 levels were higher in males (P < .001 for each). In female and male newborns, the CD3/CD4 levels were 53.83 ± 9.46 and 16.82 ± 5.19, respectively, and the CD3/CD8 levels were 48.80 ± 8.65 and 21.48 ± 6.02, respectively. A moderate negative correlation was found between CD3/CD4 and CD3/CD8 in female and male newborns (rfemale = -0.488, rmale = -0.574, P < .001). CONCLUSION: This study showed that although there were no differences in the lymphocyte subsets in newborns with BTD, the CD3/CD4 levels were higher in females, and the CD3/CD8 levels were higher in males. In addition, there was a negative correlation between the CD3/CD4 and CD3/CD8 levels in both genders. Although these results indicate sexual dimorphism between CD3/CD4 and CD3/CD8 levels, whether this dissociation is unique to BTD in newborns is not fully clear.
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Deficiência de Biotinidase , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Recém-Nascido , Células Matadoras Naturais , Contagem de Linfócitos , Subpopulações de Linfócitos , Masculino , Subpopulações de Linfócitos TRESUMO
AIM: It is challenging to evaluate reproductive potential during childhood. These challenges necessitate the use of invasive dynamic tests. Although the anti-Mullerian hormone (AMH) is a reliable biomarker in evaluating testicular function, especially in the pre-pubertal period, there are uncertainties concerning its use in a clinical setting. This study is focused on comparing the AMH and human chorionic gonadotropin (hCG) test in boys with hypogonadism. METHODS: A total of 160 boys aged between 0 and 18 years who presented with complaints associated with hypogonadism were prospectively enrolled in the study. All children were assigned to the following five groups: gonadal disorders (n = 34), androgen synthesis and end organ effect disorder (n = 48), isolated genital malformation disorders (n = 57), hypogonadotropic hypogonadism (n = 15) and constitutional delayed puberty (n = 6). All children underwent a short 3-day hCG test (1500 U/m2 /day). The concordance and correlation were evaluated between the hCG test and AMH. RESULTS: All groups exhibited a strong correlation (r160 = 0.689) and strong concordance (Kappa coefficient160 = 0.7) between the AMH and hCG test. Values of AMH higher than 32.7 pmol/L and hCG responses higher than 86 pmol/L were significant as indicative markers of functional testicular tissue presence. CONCLUSIONS: This study has shown that there is a strong correlation between the AMH and short-term hCG test and that values of AMH higher than 32.7 pmol/L and stimulated testosterone higher than 86 pmol/L can be used as indicators of functionally sufficient testicular tissue. These results indicate that AMH value can be used as a reliable and useful biomarker in the evaluation of the testicular function in 46 XY hypogonadism.
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Hormônio Antimülleriano , Hipogonadismo , Adolescente , Criança , Pré-Escolar , Gonadotropina Coriônica , Humanos , Hipogonadismo/diagnóstico , Lactente , Recém-Nascido , Masculino , Testículo , TestosteronaRESUMO
AIM: Although newly diagnosed type 1 diabetes mellitus (T1DM) occurs sporadically in childhood, there is an increased risk of T1DM for first-degree relatives of patients that endure into the advanced years. Determination of T1DM incidence in siblings of children with T1DM helps predict the development of new cases. This study focuses on the incidence of the disease in siblings of children with T1DM. METHOD: A total of 1497 siblings of 850 children (403 female; 447 male) diagnosed with T1DM between 2007 and 2018 years were retrospectively screened for T1DM. The patients were divided into four onset age groups: 0-4, 5-9, 10-14 and ≥15. The annual incidence was calculated for the region. RESULTS: A total of 34 siblings diagnosed with T1DM were detected. The incidence relating to the years investigated was between 7.42 and 11.73/100 000 for the newly diagnosed indexes while it ranged between 0 and 5.8% for siblings. The 5-9 year group was the most commonly diagnosed onset age group in index (n = 312) and siblings (n = 20). For siblings, the male sex and 5-9 aged at diagnosis of index were significant risk factors for development of T1DM (OR:2.35 and 2.85). CONCLUSION: This study shows that in the first years following the diagnosis of an index, incidence of T1DM among the siblings can rise up to 5.8%, and the age group of 5-9 in the index and the male sex in the sibling are the most important risk factors. These findings show that the risk for siblings of children with T1DM remarkably increases in the first years after diagnosis in index cases.
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Diabetes Mellitus Tipo 1 , Idoso , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , IrmãosRESUMO
PURPOSE: 17α Hydroxylase/17,20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia, typically diagnosed in late adolescence with symptoms of pubertal delay and hypertension. This study aimed to determine the clinical and laboratory characteristics of 17OHD cases and gather data on disease management. METHODS: Data from 97 nationwide cases were analyzed using the CEDD-NET web system. Diagnostic, follow-up findings, and final heights of patients were evaluated. RESULTS: Mean age at admission was 13.54 ± 4.71 years, with delayed puberty as the most common complaint. Hypertension was detected in 65% at presentation; hypokalemia was present in 34%. Genetic analysis revealed Exon 1-6 homozygous deletion as the most frequent mutation, identified in 42 cases. Hydrocortisone replacement was universal; pubertal replacement was administered to 66 cases. Antihypertensive treatment was required in 57 (90%) patients. Thirty-seven cases reached final height, with an average SD of 0.015 in 46,XX and -1.43 in 46,XY. Thelarche and pubarche did not develop properly in some cases despite estradiol treatment. CONCLUSION: This study represents the largest cohort of pediatric cases of 17-hydroxylase deficiency (17OHD) documented in the literature. Hypertension and hypokalemia can serve as guiding indicators for early diagnosis.The final height is typically considered to be normal. The relationship between genotype and phenotype remains elusive. The initial genetic test for exon 1-6 deletions may be MLPA in our region.
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Hiperplasia Suprarrenal Congênita , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Hiperplasia Suprarrenal Congênita/genética , Estudos de Coortes , Hipertensão/genética , Hipopotassemia/genética , Puberdade Tardia/genética , Esteroide 17-alfa-Hidroxilase/genética , Turquia/epidemiologiaRESUMO
Introduction: There have been some significant changes regarding healthcare utilization during the COVID-19 pandemic. Majority of the reports about the impact of the COVID-19 pandemic on diabetes care are from the first wave of the pandemic. We aim to evaluate the potential effects of the COVID-19 pandemic on the severity of diabetic ketoacidosis (DKA) and new onset Type 1 diabetes presenting with DKA, and also evaluate children with DKA and acute COVID-19 infection. Methods: This is a retrospective multi-center study among 997 children and adolescents with type 1 diabetes who were admitted with DKA to 27 pediatric intensive care units in Turkey between the first year of pandemic and pre-pandemic year. Results: The percentage of children with new-onset Type 1 diabetes presenting with DKA was higher during the COVID-19 pandemic (p < 0.0001). The incidence of severe DKA was also higher during the COVID-19 pandemic (p < 0.0001) and also higher among children with new onset Type 1 diabetes (p < 0.0001). HbA1c levels, duration of insulin infusion, and length of PICU stay were significantly higher/longer during the pandemic period. Eleven patients tested positive for SARS-CoV-2, eight were positive for new onset Type 1 diabetes, and nine tested positive for severe DKA at admission. Discussion: The frequency of new onset of Type 1 diabetes and severe cases among children with DKA during the first year of the COVID-19 pandemic. Furthermore, the cause of the increased severe presentation might be related to restrictions related to the pandemic; however, need to evaluate the potential effects of SARS-CoV-2 on the increased percentage of new onset Type 1 diabetes.
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BACKGROUND/AIM: Maturity-onset diabetes of the young (MODY) is often misdiagnosed as other types of diabetes because it is overlooked due to atypical clinical presentations. This study aims to reveal the clinical and laboratory clues and examine their compatibility with MODY genotypes. METHODS: Participants consisted of 230 children with atypical presentations for type1(T1DM) and type2 diabetes mellitus (T2DM). MODY-causing mutations were screened in the following genes:GCK-HNF1A-HNF4A-HNF1B-PDX1-NEUROD1-KLF11-CEL-PAX4-INS-BLK. Clinical and laboratory features were compared between children with MODY and children without MODY. RESULTS: The most common reasons for MODY screening were as follows (n/%):low daily dose of insulin (DDI) requirement (122/53%), absence of beta-cell antibodies(58/25.3%), coincidental hyperglycemia(26/11.3%), family history of diabetes (12/5.2%), hypoglycemia/hyperglycemia episodes(7/3%), hyperglycemia related to steroids(3/1.4%) and renal glycosuria(2/0.8%). The markers with the most likelihood to distinguish MODY from T1DM were determined as follows: measurable C-peptide in follow-up, family history of early-onset diabetes and low DDI requirement (odds ratio:12.55, 5.53 and 3.43, respectively). The distribution of the most common causative genes in children with MODY(n = 24) is as follows (n/%):GCK(15/62.5%), HNF4A(7/29.1%), HNF1A(1/9.2%) and PDX1(1/9.2%).All children(n = 12) with GCK-MODY(MODY2) were screened for low DDI requirement, while beta-cell negativity was more common in HNF4A-MODY(MODY1). CONCLUSION: The study shows that measurable C-peptide in follow-up, family history of early-onset diabetes, and low DDI are still remarkable clues to predict MODY in children with misdiagnosed T1DM. In addition, the most common mutations were found in the GCK and HNF4A genes. Among children misdiagnosed with T1DM, a low DDI requirement was found more frequently in MODY2, whereas beta-cell antibody negativity was more common in MODY1.
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Peptídeo C/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Predisposição Genética para Doença , Quinases do Centro Germinativo/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/genética , Mutação , Adolescente , Criança , Pré-Escolar , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Lactente , MasculinoRESUMO
OBJECTIVE: Energy balance is preserved through the exchange between body weight and adipose tissue across the multi-faceted complex network that is composed of the sensorial, metabolic, and neuro-endocrine circuits. The olfactory control of energy homeostasis is maintained through the interplay between the olfactory bulb (OB) and adipose tissue. While extremely studied, most researches still report controversial results and sensorial regulation of obesity is not fully understood. This study aims to investigate the interplay between olfactory bulb volume (OBV) as a radiological clue of sensorial control and obesity in children. SUBJECTS AND METHOD: Children (n = 195) were classified into four groups based on body mass index (BMI) percentiles: normal weight (n = 89), overweight (n = 31), obese (n = 32) and morbidly obese (n = 43). OBV were calculated using MRI. RESULTS: Mean OBV was higher in children with obesity than in those of normal weights. The means of OBV are found higher in the overweight and obese children (43.76 ± 9.50-49.29 ± 8.61 mm3) than in those of morbidly obese (38.23 ± 11.52 mm3) (p < 0.001). In overweight and obese children, a positive correlation were found between the BMI and OBV (roverweigh = 0.275-robese = 0.377), while in the morbidly obese group, there was a negative correlation (rseverelyobese = -0.445). CONCLUSION: This study reveals that OBV is higher in obese children. Also, it shows that there is a positive correlation between OBV and BMI in overweight and obese children and a negative correlation in the morbidly obese group. These radiological bimodal changes in OBV indicate that olfactory control acts to provide energy balance, mediated by positive in the overweight and obese children, negative feedback in the morbidly obese group.
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Obesidade Mórbida , Obesidade Infantil , Índice de Massa Corporal , Criança , Humanos , Obesidade Mórbida/complicações , Bulbo Olfatório/diagnóstico por imagem , Sobrepeso/complicações , Obesidade Infantil/diagnóstico por imagem , OlfatoRESUMO
Background The olfactory bulb (OB) and eyeball size change depending on age and puberty. There is a well-established trade-off between sensory structures of the brain such as the eye and the olfactory bulb that depend on environmental circumstances in the evolutionary history of animals. The aim of this study was to developmentally investigate the potential reciprocal changes between OB and eyeball volumes (EV) in girls with precocious puberty (PP). Methods A total of 148 girls aged between 5 and 8 years (63 PP, 85 healthy) were included in the study. Exclusion criteria: Cases of anosmia/hyposmia, neurodegenerative disorder, refractive errors and trauma. The pituitary height (PH), EV and OB volumes were measured on segmentation of a magnetic resonance image (MRI) slice using manual countering. The corrected measurements by body surface were used in all statistical analyses. Results In girls with PP, the means of the OB volume and PH were larger (71.11 ± 20.64 mL) and higher (4.62 ± 1.18 mm), respectively, while the mean of EVs was smaller (11.24 ± 2.62 cm3) (p = 0.000). Cut-off values were 62.27 mL, 10.7 cm3 and 4.71 mm for OB volume, EV and PH, respectively. While negative correlations were found between OB volume-EV and EV-PH (r63 = -0.224, p = 0.001 and r63 = -0.116, p = 0.001, respectively), OB volume was positively correlated with PH (r63 = 0.578, p = 0.001). Conclusions The present study demonstrates that girls with PP have significantly larger OB volume, but smaller EV, and there is negative correlation between the two structures. These results indicate that there is trade-off between anatomical dimensions of OB and eyeball in favor of OB in PP girls.
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Olho/anatomia & histologia , Bulbo Olfatório/anatomia & histologia , Puberdade Precoce/fisiopatologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Tamanho do Órgão , Prognóstico , Estudos Retrospectivos , Maturidade SexualRESUMO
Childhood obesity is a growing public health burden in many countries. The lipid perilipin 1 (PLIN1) gene is involved in regulation of lipolysis, and thus represents a viable candidate mechanism for obesity genetics research in children. In addition, the regulation of candidate gene expression by circulating microRNAs (miRNAs) offers a new research venue for diagnostic innovation. We report new findings on associations among circulating miRNAs, regulation of the PLIN1 gene, and susceptibility to childhood obesity. In a sample of 135 unrelated subjects, 35 children with obesity (between ages 3 and 13) and 100 healthy controls (between ages 4 and 16), we examined the expression levels of four candidate miRNAs (hsa-miR-4777-3p, hsa-miR-642b-3p, hsa-miR-3671-1, and hsa-miR-551b-2) targeting the PLIN1 as measured by real-time polymerase chain reaction in whole blood samples. We found that the full genetic model, including the four candidate miRNAs and the PLIN1 gene, explained a statistically significant 12.7% of the variance in childhood obesity risk (p = 0.0034). The four miRNAs together explained 10.1% of the risk (p = 0.008). The percentage of variation in childhood obesity risk explained by hsa-miR-642b-3p and age was 19%. In accordance with biological polarity of the observed association, for example, hsa-miR-642b-3p was upregulated, while the PLIN1 expression decreased in obese participants compared to healthy controls. To the best of our knowledge, this is the first clinical association study of these candidate miRNAs targeting the PLIN1 in childhood obesity. These data offer new molecular leads for future clinical biomarker and diagnostic discovery for childhood obesity.
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Biomarcadores , MicroRNA Circulante , Regulação da Expressão Gênica , MicroRNAs/genética , Obesidade Infantil/etiologia , Perilipina-1/genética , Interferência de RNA , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , MicroRNAs/sangue , Obesidade Infantil/sangueRESUMO
Background The genotype-phenotype relationship shows regional variability in 21-hydroxylase deficiency (21-OHD) caused by mutations in the CYP21A2 gene. This study focuses on the genotype-phenotype compatibility between patients and their siblings in a region where consanguineous marriage is common. Methods The most common mutations (I2G-P30L-I172N-V237E-M239K-V281L-Q318X-R356W-F306 + nt) were studied in 60 children with 21-OHD and 40 siblings (12 symptomatic and 28 asymptomatic; mean age 5.89 ± 4.63 and 8.34 ± 2.22 years, respectively). The allele number (patients; 93 siblings; 70 alleles) was counted for each case. Salt wasting (SW; n = 38), simple virilizing (SV; n = 11) and non-classical congenital adrenal hyperplasia (NCCAH; n = 11) types were compared with their genotypes classified into groups Null-AB-C-D-E based on enzyme impairment. Results Disease-causing mutations were identified in unrelated alleles: 80 out of 93 alleles (86%) in the patients: SW, 51/56 (91%); SV, 14/16 (87.4%) and NCCAH, 15/21 (71.4%). There were 43 out of 70 alleles (61.4%) in the siblings (asymptomatic, 25/50 [50%]; symptomatic, 18/20 [90%]). The most frequently detected mutations in the patients were: I2G (22%), Q318X-P30L-V281L (13% each). The distribution of the most common mutations by clinical types was: SW: I2G-Q318X (30.2%-19.6%), SV: I172NI2G (37.5%-18.7%), NCCAH: V281L-P30L (33.3%-28.5%). In patients and symptomatic siblings, the concordance percentages by genotype groups were: Null (100%-100%), A (85%-60%), B (100%-Not applicable), C (41.6%-50%). Eleven out of 28 asymptomatic siblings had disease-causing mutations (four, severe; one, moderate; six, mild). The distribution of genotypes by phenotypes were: SW: Null-A (88%), SV: B-A (50%-41.6%), NCCAH: C (100%). Conclusions This study showed that the most common alleles were IN2G-Q381X-R356W-P30L-V281L in the children with 21-OHD and asymptomatic siblings, and that the phenotype can be predicted from the genotype except for the P30L-V281L. This result suggests that the most common mutations in 21-OHD are similar to previous reports, but that the genotype-phenotype compatibility is good except for group C showing regional variability, and that genotyping of siblings discovered new patients.
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Hiperplasia Suprarrenal Congênita/genética , Mutação , Esteroide 21-Hidroxilase/genética , Adolescente , Hiperplasia Suprarrenal Congênita/epidemiologia , Alelos , Criança , Pré-Escolar , Feminino , Seguimentos , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Prevalência , Prognóstico , Estudos Retrospectivos , Irmãos , TurquiaRESUMO
Background/objective The olfactory bulb (OB) and pubertal development have a close relationship as they share a common ontogenetic origin. The aim of this study was to analyze the potential relationship between precocious puberty (PP) in girls as a sign of early pubertal timing and their OB volume as an indicator of its functional activity. Design In the study group (n = 125), OB volume, pituitary height (PH), body mass index (BMI) and body surface (S) variables were retrospectively investigated in 49 girls included in the PP group and 76 healthy girls constituting the control group. Volumetric and length measurements were performed on a magnetic resonance imaging (MRI) scan by using manual segmentation of slices. Results The mean OB volume (73.41 ± 17.21 mm3) and PH (4.96 ± 1.01 mm) were significantly higher in the PP group (p = 0.001 and p = 0.001, respectively). The mean volume difference between the right and left bulbs (1.52 ± 1.87) was higher in the PP group (p = 0.03). The body surface (1.05 ± 0.16 m2) was larger in the PP group (p = 0.09). There was a high correlation between the OB volume and PH (r125 = 0.716). There was a moderate correlation between the body surface and OB volume (r125 = 654), and a weak correlation between the former (S) and the PH (r125 = 452). Conclusions This study showed that there is a strong correlation between increased OB volume and PH in cases with PP. It indicates that increased OB volume may be a strong clue that olfactory functions play a role in pubertal timing in humans, although it does not show definitive proof of a causal relationship.
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Nariz/anatomia & histologia , Bulbo Olfatório/anatomia & histologia , Puberdade Precoce/patologia , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Tamanho do Órgão , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: Viruses trigger and promote islet cell destruction and cause type 1 diabetes mellitus (T1DM). However, the existence of a cause-and-effect relationship is under debate. The aim of this study is to investigate the sero-epidemiological and molecular evidence on enteroviruses and respiratory viruses in patients with newly diagnosed T1DM during the cold season. DESIGN: Forty children newly diagnosed with T1DM and 30 healthy children who presented to the clinic over the course of a year were included in the study. The IgM antibodies against enteroviruses and respiratory viruses were studied using the indirect immunofluorescence assay (IFA) test, and no CBV4-specific RNA was detected in the children. The onset times of T1DM were classified into fall-winter and spring-summer seasons and separated into cold, moderate, or warm months in terms of temperature. RESULTS: The percentages of viral IgM antibodies against most common viruses were detected in the patients as follows: influenza B (IVB) (70%), echovirus 7 (ECHO7) (45%), parainfluenza virus 4 (PIV4) (40%), coxsackievirus A7 (CAV7) (27.5%), and H3N2 (22.5%). Compared with the control group, the above viruses had a significant association with T1DM (p ≤ 0.001, p ≤ 0.001, p = 0.035, p = 0.003, and p = 0.023, resp.). CBV4-specific RNA was not detected in any serum. A total of 75% and 95% patients were diagnosed with T1DM in the fall-winter seasons and cold-moderate months, respectively. CONCLUSION: Our study demonstrates the significant association between T1DM and the presence of IgM antibodies against IVB, ECHO7, PIV4, CAV7, and H3N2, and the majority of newly diagnosed T1DM appeared in the fall-winter season. It suggests that enteroviruses and respiratory viruses, in addition to seasonal variation, could play a role in the etiopathogenesis and clinical onset of T1DM.
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Anticorpos Antivirais/imunologia , Diabetes Mellitus Tipo 1/virologia , Infecções por Enterovirus/virologia , Enterovirus/imunologia , Imunoglobulina M/imunologia , Infecções Respiratórias/virologia , Adolescente , Fatores Etários , Anticorpos Antivirais/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/imunologia , Enterovirus/patogenicidade , Infecções por Enterovirus/sangue , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/imunologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Imunoglobulina M/sangue , Lactente , Masculino , Infecções Respiratórias/sangue , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/imunologia , Estudos Retrospectivos , Fatores de Risco , Estações do Ano , Fatores de Tempo , TurquiaRESUMO
PURPOSE: The aim of this study is to investigate the effects of HBsAg vaccine and levamisole on virological indicators in naive patients suffering from chronic hepatitis B (CHB) and in healthy carriers of hepatitis B. METHOD: Vaccination and treatment with levamisole were applied to 93 minor patients in total, 43 of them inactive CHB carriers and 50 patients suffering from CHB. RESULTS: 15 (30%) of 50 patients who had high ALT values in the beginning of the study had normal values after treatment. In nine (12%) patients, posttreatment ALT values were higher than pretreatment values, and six (10%) patients showed HBV-DNA loss. In spite of the presence of 50 (54%) HBeAg-positive patients before treatment, 17 (34%) patients proved to be HBeAg-negative after treatment. HBeAg sero-conversion was seen in 10 (20%) cases. In two (2%) patients, HBsAg sero-conversion occurred. CONCLUSION: It was found that treatment with levamisole and vaccine had positive effects on CHB patients and healthy carriers with respect to HBV DNA loss, HBeAg sero-conversion and ALT normalization. The viral load increases and ALT increases that occurred in certain cases were thought to be related to the early immune response. It was determined that combined levamisole and vaccine therapy had no additional positive effect.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Levamisol/uso terapêutico , Criança , Doença Crônica , Feminino , Humanos , Imunoterapia , MasculinoRESUMO
BACKGROUND/AIMS: Pathogenesis of chronic hepatitis B and hepatitis B carrier status is related to deficiencies in the immune system. Thus, treatments regulating the immune system are under discussion. The aim of this study was to investigate the effects of HBsAg vaccine and levamisole on lymphocyte subgroups and immunoglobulins in children with chronic hepatitis B and hepatitis B carriers. METHODS: A total of 93 naive children (43 chronic hepatitis B carriers, 50 chronic hepatitis B patients) were treated in three groups with HBsAg vaccine, levamisole or levamisole plus HBsAg vaccine. Levamisole (ketrax) was delivered as 2.5 mg/kg/day per os, three times per week for three months; the vaccine (Gen HevacB) was administered subcutaneously as 20, 30, 40 microg at one-month intervals. Both medications were delivered at same dosages in the combined group. The examinations were performed at pre-treatment and at the end of the third month when the treatment concluded. RESULTS: After treatments, CD3, CD4 and CD4/CD8 significantly increased and CD8 significantly decreased in chronic hepatitis B patient groups, except in the levamisole treated group. IgG and IgA were significantly decreased in all groups of chronic hepatitis B patients. CONCLUSIONS: It was found that HBsAg vaccine induced cellular immunostimulation in children with chronic hepatitis B; however, levamisole did not. The immune cells of hepatitis B carriers did not manifest a significant change in any treatment group. Although there was no change in B-cell, significant decreases were determined in immunoglobulins (IgG, IgA), especially in chronic hepatitis B patients.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Portador Sadio/virologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Levamisol/uso terapêutico , Adolescente , Anticorpos Anti-Idiotípicos/imunologia , Complexo CD3/imunologia , Antígenos CD4/imunologia , Relação CD4-CD8 , Portador Sadio/imunologia , Criança , DNA Viral/análise , Quimioterapia Combinada , Feminino , Seguimentos , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Imunidade Celular/efeitos dos fármacos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Masculino , Estudos Retrospectivos , Linfócitos T/imunologia , Resultado do TratamentoRESUMO
OBJECTIVE: To assess levels of vitamin D and of immunoglobulin G subclasses in children and adolescents with type 1 Diabetes Mellitus with or without autoimmune thyroiditis. DESIGN: Among 213 patients with type 1 diabetes, the cases with thyroid-specific autoantibodies formed Group 1 [n=19, M/F: 7/12, median age 13 years (10.1-14.7)]. Nineteen age-, gender-, and diabetes duration-matched cases with type 1 diabetes without any other systemic disease were designated as controls [Group 2, M/F: 7/12, median age 12.9 years (10.5-14.9)]. RESULTS: Levels of thyroid hormones, vitamin D, total IgG and IgG subclasses, as well as IgG subclasses/total IgG ratios were similar between the groups. Five cases (26%) in Group 1 had IgG4 levels > + 2 SDS, whereas there were no such cases in Group 2 (p=0.046). These five patients had similar clinical features but higher median IgG4 levels and IgG4/Total IgG ratios compared to the subjects with IgG4 levels < + 2 SDS in Group 1 and Group 2. CONCLUSIONS: There was no difference of vitamin D levels between the groups. Only a small percentage of patients with type 1 diabetes also having autoimmune thyroiditis had elevated serum IgG4 levels, revealing the heterogeneity of autoimmune thyroiditis and existence of IgG4 thyroiditis in the pediatric age group. Total IgG, the other IgG subclasses, and vitamin D levels did not differ in patients with autoimmune thyroiditis and type 1 diabetes compared to those suffering only from type 1 diabetes.