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Objective: Maturity-onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY. Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated. Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A; 8 (3.6%) HNF4A, 8 (3.6%) KLF11 and 7 (3.1%) HNF1B. The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n=3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral antidiabetic treatment. Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only.
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INTRODUCTION & OBJECTIVE: 3 M Syndrome is a rarely encountered autosomal recessive syndrome characterized by low birth weight, severe postnatal growth deficiency, and minor dysmorphic abnormalities. 3 M-related short stature has been attributed to the resistance to growth hormone (GH) to a certain extent rather than to GH deficiency. The resistance to GH, on the other hand, has been associated with impaired protein scaffolding, transport, and p53-mediated apoptosis at the IGF-1 post-receptor pathway. In this context, the objective of this study is to evaluate the clinical, laboratory, and genetic characteristics of the patients with 3 M syndrome, detect the mutations frequently observed in these patients, and assess their response to GH treatment. MATERIAL&METHODS: The sample of this single-center study consisted of patients diagnosed with 3 M syndrome based on genetic tests between 2007 and 2021. Patients' clinic, laboratory, and genetic characteristics pertaining to the time of admission and follow-up were recorded. All patients except one underwent a growth hormone stimulation test (GHST) (Levo-dopa or insulin tolerance test). Insulin-like growth factor (IGF) generation test was performed on those with sufficient GHST results (0.1 mg/kg/day for four days). RESULTS: The median age of the patients, five females and three males, was 2.8 (0.25-8.12) years at admission. All but one patient were small for gestational age (SGA). The patient with normal birth weight was the baby of a diabetic mother. Obscurin-like 1 (OBSL1) variant was detected in all cases. The median height standard deviation score (SDS) at admission was -4.94 ((-5.63)- (-3.27)) SDS, and the median midparenteral height SDS was -1.27 SDS ((-3.1)- (0.34)). All patients were prepubertal at admission. The GHST response was sufficient in five cases. IGF generation test was performed in three cases. Seven patients received GH therapy (35-57 µg/kg/day). Five of these patients discontinued GH therapy since their growth velocity (GV) fell below normal during treatment. In addition, one case discontinued GH therapy because her IGF-1 value was>2 SDS, and another case received gonadotropin-releasing hormone (GnRH) analogs together with GH therapy. The median age and height SDS of the patients were 10.1 (1.79-18) years and -5.09 SDS ((-7.11)- (2.45)), respectively, as of the last follow-up visit. The height SDS values of the two cases that reached the final height were -7.11 SDS and -3.39 SDS. There were no side effects of GH treatment. CONCLUSION: The study findings indicated a good GV during the early stages of the long-term GH treatment administered to patients with 3 M syndrome. However, response to GH therapy decreased in the following years, and the desired improvement in height SDS could not be achieved in patients who reached their final heights. Taken together with the literature data, it has been concluded that initiating GH therapy in the prepubertal period provided better outcomes than after puberty.
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Hormônio do Crescimento , Hormônio do Crescimento Humano , Masculino , Feminino , Humanos , Pré-Escolar , Criança , Hormônio do Crescimento/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like I/uso terapêutico , Hormônio do Crescimento Humano/uso terapêutico , Transtornos do Crescimento , Estatura , Proteínas do CitoesqueletoRESUMO
OBJECTIVE: The onset of puberty in children is occurring at an increasingly earlier ages. During the coronavirus 2019 pandemic, children experienced epidemic-related changes such as stress, sedentary lifestyle, and weight gain. MATERIALS AND METHODS: Auxological, clinical, endocrinological, and radiological data in the files of 57 patients who were given gonadotropin-releasing hormone analog therapy with the diagnosis of central precocious puberty between April 1 and July 1, 2019 (group 1) and April 1 and July 1, 2020 (group 2) were analyzed retrospectively. RESULTS: A total of 27 patients (26 girls, 1 boy) in group 1 and 30 patients (28 girls, 2 boys) in group 2 were diagnosed with central precocious puberty. Mean ages at diagnosis for groups 1 and 2 were 28.54 ± 0.94 and 7.92 ± 0.96 years, respectively (P = .018). Mean bone age at diagnosis for group 1 was 9.78 ± 1.48 (6.8-12), and for group 2 it was 8.78 ± 1.11 (6.5-12) years (P = .013). The mean age of starting treatment in groups 1 and 2 was 8.94 ± 0.17 (6.8-9.8) and 8.07 ± 0.02 (5.8-10) years, respectively (P = .002). Average birth weights for groups 1 and 2 were 950 ± 1100 (2300-3400) and 3180 ± 717 (870-3820) g, respectively (P = .012). Treatment was started when breast stage was T3 in 57.69% of group 1 and T2 in 75% of group 2, and a statistical difference was found between them (P = .006) and uterine length was higher in group 2 (P = .144). CONCLUSION: During the coronavirus 2019 pandemic, patients who start central precocious puberty therapy were of younger age. In our single-center experience, coronavirus 2019 was not seen to have a significant impact on central precocious puberty.
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OBJECTIVES: Nutritional rickets (NR) is still an important problem and one which increasing influxes of immigrants are further exacerbating. This study evaluated cases of mostly immigrant children followed up with diagnoses of NR in our pediatric endocrinology clinic. METHODS: Details of 20 cases diagnosed with NR between 2017 and 2020 were retrieved from file records. RESULTS: Twenty (11 male) cases were included in the study. Three (15%) were Turkish nationals and the others (85%) were immigrants. Hypocalcemia and hypophosphatemia were detected in 17 and 13, respectively. Alkaline phosphatase (ALP) values were normal in two cases, while ALP and parathyroid hormone (PTH) values were elevated in all other cases, and PTH levels were very high (473.64 ± 197.05 pg/mL). 25-hydroxyvitamin D levels were below 20 ng/mL in all cases. Patients with NR received high-dose long-term vitamin D or stoss therapy. Six patients failed to attend long-term follow-up, while PTH and ALP levels and clinical findings improved at long-term follow-up in the other 14 cases. CONCLUSIONS: The elevated PTH levels suggest only the most severe cases of NR presented to our clinic. Clinically evident NR is therefore only the tip of the iceberg, and the true burden of subclinical rickets and osteomalacia remains unidentified. Public health policies should therefore focus on universal vitamin D supplementation and adequate dietary calcium provision, their integration into child surveillance programs, adequate advice and support to ensure normal nutrition, exposure to sunlight, and informing families of the increased risk not only for resident populations but also for refugee and immigrant children.
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Emigrantes e Imigrantes , Raquitismo/prevenção & controle , Adolescente , Fosfatase Alcalina/metabolismo , Cálcio da Dieta/administração & dosagem , Criança , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos , Lactente , Masculino , Hormônio Paratireóideo/sangue , Raquitismo/sangue , Raquitismo/epidemiologia , Vitamina D/administração & dosagemRESUMO
Testicular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART. METHOD: Among 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded. RESULTS: TART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro). CONCLUSION: We found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype-phenotype correlation in TART may benefit further investigations in larger series.
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Hiperplasia Suprarrenal Congênita , Tumor de Resto Suprarrenal , Neoplasias Testiculares , Masculino , Humanos , Hiperplasia Suprarrenal Congênita/genética , Tumor de Resto Suprarrenal/genética , Tumor de Resto Suprarrenal/diagnóstico , Esteroide 11-beta-Hidroxilase/genética , Genótipo , Neoplasias Testiculares/genética , Neoplasias Testiculares/diagnóstico , Mutação , Esteroide 21-Hidroxilase/genéticaRESUMO
In recent years, interest in the evaluation of vitamin D levels and the possible outcomes of their deficiency during pregnancy has increased. However, there is no consensus on when to start vitamin D supplementation, its duration, dosage, and the optimum level during pregnancy. The toxicity of vitamin D is as important as its deficiency. From the history of a 5-day-old male baby who was investigated for hypercalcemia, it was learned that the mother took 300,000 IU vitamin D-five ampoules/oral at 30 weeks of gestation every other day. The infant was born prematurely, postpartum bradycardia required positive pressure ventilation, and his hypercalcemia lasted approximately 4 months despite treatment. Maternal excessive and inappropriate use of vitamin D can cause preterm labor and severe hypercalcemia, which is a life-threatening complication in the neonatal period. This case is presented to draw attention to the negative effects of maternal high-dose vitamin D during pregnancy.
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Objective: Familial hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive disease caused by a mutation in the transient receptor potential melastatin 6 (TRPM6) gene and is characterized by selective magnesium malabsorption. Affected cases are usually diagnosed during infancy and usually present with seizures due to hypocalcemia and hypomagnesemia. Irreversible neurological deficits and arrhythmias can be observed without appropriate treatment. The aim was to evaluate the long-term follow-up of patients with genetically confirmed HSH. Methods: A total of six patients with HSH, two of whom were siblings, were included. Age at diagnosis, clinical, laboratory and follow-up data on admission were recorded. All 39 exons of the TRPM6 gene and flanking exon-intron junctions from genomic DNA were amplified and sequenced in all cases. Results: The median (range) follow-up duration was 12.1 (7.6-21.7) years. All cases were diagnosed in infancy. Four different mutations, three of which had not been previously reported, were detected in the TRPM6 gene. Treatment compliance was good and there were no severe complications in the long-term follow-up of cases. However, mental retardation, specific learning difficulty and attention deficit/hyperactive disorder were observed as comorbidities. Conclusion: Of the four different TRPM6 mutations in this small cohort, three had not been previously reported. The long-term prognosis of HSH appears to be good, given early diagnosis and good treatment compliance. This long-term follow-up and prognostic data and the three novel mutations will contribute to the published evidence concerning this rare condition, HSH, and it is hoped will prevent negative outcomes.
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Hipocalcemia/genética , Deficiência de Magnésio/congênito , Mutação , Canais de Cátion TRPM , Adolescente , Fatores Etários , Criança , Desenvolvimento Infantil , Pré-Escolar , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/tratamento farmacológico , Hipocalcemia/metabolismo , Lactente , Compostos de Magnésio/uso terapêutico , Deficiência de Magnésio/diagnóstico , Deficiência de Magnésio/tratamento farmacológico , Deficiência de Magnésio/genética , Deficiência de Magnésio/metabolismo , Masculino , Fenótipo , Estudos Retrospectivos , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Prohormone convertase 1/3, encoded by the proprotein convertase subtilisin/kexin type 1 gene, is essential for processing prohormones; therefore, its deficiency is characterized by a deficiency of variable levels in all hormone systems. Although a case of postprandial hypoglycemia has been previously reported in the literature, prohormone convertase insufficiency with type 2 diabetes mellitus has not yet been reported. Our case, a 14-year-old girl, was referred due to excess weight gain. She was diagnosed as having type 2 diabetes mellitus based on laboratory test results. Prohormone convertase deficiency was considered due to the history of resistant diarrhea during the infancy period and her rapid weight gain. Proinsulin level was measured as >700 pmol/L(3.60-22) during diagnosis. In genetic analysis, a c.685G> T(p.V229F) homozygous mutation in the PCSK1 gene was detected and this has not been reported in relation to this disorder. In conclusion, patients with recurrent resistant diarrhea during infancy followed by rapid weight gain need to be evaluated with the diagnosis of prohormone convertase deficiency.
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PURPOSE: To assess the visual field sensitivity changes and investigate the association between visual field sensitivity and retinal nerve fiber layer thickness in patients with type 1 diabetes mellitus. MATERIALS AND METHODS: In this cross-sectional and observational study, 46 patients (22 males, 24 females) with type 1 diabetes mellitus and no diabetic retinopathy formed the diabetes mellitus group and 50 age-matched healthy subjects (32 males, 18 females) formed the control group. Retinal nerve fiber layer thickness, full-threshold standard automated perimetry, and short-wavelength automated perimetry were performed. Main outcomes were retinal nerve fiber layer thickness, mean deviation, pattern standard deviation, and short fluctuation. RESULTS: Average retinal nerve fiber layer thickness was significantly thinner in the diabetes mellitus group (p < 0.001). The mean values of mean deviation and pattern standard deviation of the full-threshold standard automated perimetry did not differ between the groups (p = 0.179, p = 0.139, respectively). Mean short fluctuation was significantly greater in the diabetes mellitus group (p < 0.001). Both mean deviation and pattern standard deviation of the short-wavelength automated perimetry were significantly greater in the diabetes mellitus group (p < 0.001, p < 0.001, respectively). Pattern standard deviation of short-wavelength automated perimetry equal or higher than 1.57 dB had 91% sensitivity and 90% specificity (area under the curve = 0.969, p < 0.001) and short fluctuations of full-threshold standard automated perimetry equal or higher than 0.80 dB had 80% sensitivity and 76% specificity over detecting early retinal nerve fiber layer loss in patients with type 1 diabetes mellitus (area under the curve = 0.855, p < 0.001). CONCLUSION: This study showed that thinner retinal nerve fiber layer in patients with type 1 diabetes mellitus may be associated with abnormal retinal sensitivity to short-wavelength stimulations in short-wavelength automated perimetry; however, retinal sensitivity to white stimulus was similar to that in healthy subjects in full-threshold standard automated perimetry.
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Diabetes Mellitus Tipo 1/fisiopatologia , Retina/patologia , Campos Visuais/fisiologia , Adolescente , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/etiologia , Retinopatia Diabética/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Fibras Nervosas/patologia , Testes de Campo Visual , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to assess initial changes in blood flow parameters of the ophthalmic artery (OA) in pediatric patients with type 1 diabetes mellitus (DM). METHODS: Sixty-three subjects were included in this prospective, cross-sectional, observational study. Thirty-one (49.2%) patients with type 1 DM without diabetic retinopathy formed the DM group. The control group comprised 32 (50.8%) healthy subjects. The OA of all of the patients was examined with Doppler ultrasonography. The main outcomes were peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) measurements. RESULTS: The mean age at onset of type 1 DM was 10.7±2.0 years and the mean duration was 11.4±11.0 months. The mean PSV and EDV outcomes in both eyes were significantly higher in the control group than in the DM group, whereas, the mean PI and RI outcomes in both eyes were significantly higher in the DM group (p<0.05). A mean RI of ≥0.75 indicated vascular hemodynamic changes associated with type 1 DM with a sensitivity of 72% and a specificity of 65% (area under the curve: 0.702; p=0.007). A mean PI of ≥1.69 predicted vascular hemodynamic changes associated with type 1 DM with a sensitivity of 79% and a specificity of 71% (area under the curve: 0.742; p=0.001). CONCLUSION: The results of this study revealed that disturbances in ocular hemodynamics might be present as early as the first year after a type 1 DM diagnosis. Changes in ocular hemodynamic parameters could be used to predict or screen for the development of vascular changes.
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AIMS AND OBJECTIVE: This study aimed to investigate the value of Thiol/Disulfide homeostasis in pediatric diabetic ketoacidosis patients suffering from type 1 diabetes mellitus. MATERIALS AND METHODS: This study featured children who were diagnosed with diabetic ketoacidosis and who were consecutively admitted to pediatric intensive care within one year of their diagnosis. Thiol/disulfide homeostasis was evaluated in 45 pediatric patients suffering from DKA, as well as 45 healthy controls of parallel gender and age. Thiol/disulfide homeostasis parameters were measured using a novel automated measurement method and the correlation between demographic data and parameters was measured. RESULTS: Pediatric patients were found to have low native thiols, total thiols and disulfide levels with type 1 diabetes after DKA (331.82±106.40, 362.71±113.31, 17.02±5.33 µmol/L, respectively) as compared to the control group (445.08±24.41, 481.21± 28.47, 18.06±5.12 µmol/L, respectively). CONCLUSION: Thiol/disulfide homeostasis was distorted in pediatric patients with DKA. Furthermore, it was found that they are not likely to return to normal, immediately after treatment.
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Diabetes Mellitus Tipo 1/diagnóstico , Cetoacidose Diabética/diagnóstico , Dissulfetos/sangue , Homeostase , Compostos de Sulfidrila/sangue , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Estresse OxidativoRESUMO
Objective: Antimüllerian hormone (AMH) concentrations in mini puberty are higher than those reported for the prepubertal period. In this study we investigated AMH concentrations in infants with premature thelarche (PT). A healthy control group was used for comparison. Methods: Forty five female infants with PT, aged between one and three years and a control group consisting of 37 healthy girls in the same age range were included in the study. Bone age, pelvic ultrasonography, and concentrations of luteinizing hormone, follicle-stimulating hormone (FSH), estradiol and AMH of the patient group were evaluated. Only serum AMH concentration of the control group was evaluated. Results: Median (range) serum AMH concentrations in the subjects were 1.66 ng/mL (11.85 pmol/L) [0.15-6.32 ng/mL (1.07-45.12 pmol/L)] and were significantly lower (p=0.025) than for the control group; 1.96 ng/mL (13.99 pmol/L) [0.60-8.49 ng/mL (4.28-60.64 pmol/L)]. AMH and FSH were negatively correlated (r=-0.360, p=0.015) in infants with PT. There was no correlation between AMH and uterine size, uterine volume, endometrial thickness, fundocervical ratio, ovarian size or volume, follicle size and follicle number. Conclusion: This is the first study that investigates AMH concentrations in infants with PT. The low AMH levels in these infants and the negative correlation between AMH and FSH suggests that AMH may play a role in suppressing pubertal findings during infancy and that decreased AMH may cause PT in infancy.
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Hormônio Antimülleriano/sangue , Biomarcadores/sangue , Puberdade Precoce/sangue , Estudos de Casos e Controles , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Prognóstico , Estudos Prospectivos , Puberdade Precoce/diagnósticoRESUMO
Background Vitamin D resistant rickets (HVDRR), is a rare autosomal recessive disorder caused by vitamin D receptor (VDR) gene mutations. There is no standard treatment in HVDRR. Case report The patient was a 3-year-old girl presenting with short stature, genu varum deformity, waddling gait and alopecia. She had hypocalcemia, hypophosphatemia, hyperparathyroidism and normal 1.25-(OH)2D levels. The patient was initially treated with calcitriol and high-dose oral calcium (Ca) for 22 months. The patient was treated with continuous high dose intravenous (i.v.) Ca therapy for 4 months, following initial lack of response to oral Ca and calsitriol. At the end of the 4 months, rickets was dramatically improved and did not recur for 3 years after i.v. Ca therapy. DNA sequence analyses of the VDR gene showed a homozygous novel mutation. Conclusions We identified a novel VDR gene mutation, and we concluded that i.v. Ca therapy from the central catheter is a safe treatment in HVDRR.
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Hormônios e Agentes Reguladores de Cálcio/administração & dosagem , Cálcio/administração & dosagem , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Mutação , Receptores de Calcitriol/genética , Administração Intravenosa , Pré-Escolar , Raquitismo Hipofosfatêmico Familiar/genética , Raquitismo Hipofosfatêmico Familiar/patologia , Feminino , Humanos , PrognósticoRESUMO
Kurnaz E, Savas Erdeve S, Özgür S, Keskin M, Özbudak P, Çetinkaya S, Aycan Z. Congenital long-QT syndrome in type 1 diabetes: a unique association. Turk J Pediatr 2019; 61: 791-793. In contrast to acquired long QT syndrome (LQTS), congenital LQTS is a relatively rare channelopathy with an incidence of 1/2,500. We describe a patient found to have a prolonged QTc in the setting of newly diagnosed Type 1 DM. To the best of our knowledge, this unique association has not been previously reported. Currently, it is shown that glucose ingestion aggravated cardiac repolarization disturbances in LQT2 patients and prolonged the cardiac repolarization phase in healthy controls. Our case presented to the hospital with syncope after increased glucose level. Therefore, it seems that increased glucose level may have prolonged QTc interval and aggravated cardiac repolarization disturbances in the presented case. By this report, we want to emphasize the importance of hyperglycaemia in congenital LQTS.
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Diabetes Mellitus Tipo 1/complicações , Síndrome do QT Longo/congênito , Síndrome do QT Longo/complicações , Adolescente , Eletrocardiografia , Feminino , Humanos , Síndrome do QT Longo/diagnósticoRESUMO
Keskin M, Savas-Erdeve S, Çetinkaya S, Aycan Z. Low hemoglobin A1c levels in a patient with diabetic ketoacidosis: Fulminant type 1 diabetes mellitus. Turk J Pediatr 2018; 60: 201-205. Fulminant type 1 diabetes mellitus (FT1DM) is a clinical condition that is characterized by remarkably rapid and complete pancreatic ß-cell destruction, rapid onset of hyperglycemic symptoms followed by ketoacidosis. In most cases this process takes a few days. Although rare, there have been clinical manifestations with a prolonged progress that lasts longer than one week. This study focused on the case of a 35-monthold boy who was referred to our clinic with the diagnosis of diabetic ketoacidosis, and later had a modest elevation in hemoglobin A1c (HbA1c) levels (6.7 %) incompatible with his significantly elevated blood glucose levels. The autoantibodies against pancreatic ß-cells were negative. On the basis of these above mentioned findings, our patient was then diagnosed with fulminant type 1 diabetes mellitus. If patients with diabetic ketoacidosis have no elevation in HbA1c levels, they should be assessed for possible clinical factors that can lead to lower detectable levels of HbA1c. Furthermore, FT1DM which is characterized by very rapid and potentially fatal progression should be considered as a differential diagnosis in these patients.
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Diabetes Mellitus Tipo 1/diagnóstico , Cetoacidose Diabética/etiologia , Insulina/uso terapêutico , Glicemia/análise , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/terapia , Cetoacidose Diabética/sangue , Cetoacidose Diabética/terapia , Diagnóstico Diferencial , Progressão da Doença , Hemoglobinas Glicadas/análise , Humanos , MasculinoRESUMO
Objective: There have been recent advances in the understanding of the etiology of idiopathic central precocious puberty (iCPP) including new genetic associations. The aim of this clinical study was to determine the frequency of MKRN3 mutation in cases of familial iCPP. Methods: Potential sequence variations in the maternally imprinted MKRN3 gene were evaluated in 19 participants from 10 families using next-generation sequencing analysis. Results: MKRN3 variation was found in only one of the 19 (5.3%) subjects. The male patient, who had a medical history of precocious puberty, had a heterozygous mutation, NM_005664.3:c.630_650delins GCTGGGC (p.P211Lfs*16). The father of this patient also had a history of precocious puberty and had the same mutation. p.P211Lfs*16 is a novel variant and it was identified as probably pathogenic by in silico analysis, consistent with the clinical findings. Conclusion: Given that MKRN3 mutation was detected in only one patient, with a paternal history of precocious puberty, this reinforces the importance of accurate family history taking. The detected incidence of MKRN3 variants in our case series was much lower than reported elsewhere which suggests a need for further studies in Turkish iCPP patients.
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Puberdade Precoce/genética , Ribonucleoproteínas/genética , Criança , Feminino , Mutação da Fase de Leitura , Genótipo , Humanos , Masculino , Linhagem , Turquia , Ubiquitina-Proteína LigasesRESUMO
Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder with early-onset obesity. Investigation of this entity have increased our insight into the important role of the leptin-melanocortin pathway in energy balance. Here, we present a patient with POMC deficiency due to a homozygous c.206delC mutation in the POMC gene. We discuss the pathogenesis of this condition with emphasis on the crosstalk between hypothalamic and peripheral signals in the development of obesity and the POMC-melanocortin 4 receptors system as a target for therapeutic intervention.
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Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/metabolismo , Obesidade/diagnóstico , Obesidade/metabolismo , Pró-Opiomelanocortina/deficiência , Insuficiência Adrenal/genética , Pré-Escolar , Feminino , Humanos , Obesidade/genética , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismoRESUMO
BACKGROUND: There are different opinions about the effects of growth hormone replacement therapy (GHRT) on thyroid function and volume. This study aimed to assess the effects of GHRT on thyroid volume and function in the children and adolescents with growth hormone (GH) deficiency. METHODS: A total of 29 patients diagnosed with GH deficiency were enrolled in the study. The control group consisted of 29 cases matched for age, gender and pubertal period with the patients. Thyroid function tests and insulin-like growth factor levels were measured, simultaneously thyroid volumes were assessed by ultrasonography at the initiation period and at the end of GHRT. RESULTS: Thyroid volumes of the patient group was -0.55±1.1 standard deviations (SDs) initially; whereas at the end of 1 year it was found to be -0.29±1.29 SDs and both SDs of thyroid volumes did not differ significantly. The SDs of thyroid volume of the control group was -0.85±1.03 SDs initially and -0.72±0.85 SDs at the end of 1 year; and they did not differ significantly. On the other hand, after GHRT of 1 year, thyroid stimulating hormone (TSH) and free thyroxine (T4) levels decreased. CONCLUSIONS: It was observed that SDs of thyroid gland volumes did not change in GH deficient children and adolescents after GHRT.
Assuntos
Nanismo Hipofisário/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/uso terapêutico , Glândula Tireoide/fisiologia , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Prognóstico , Testes de Função Tireóidea , Glândula Tireoide/efeitos dos fármacos , Tireotropina/sangue , Tiroxina/sangue , Fatores de TempoRESUMO
BACKGROUND: Anti-Müllerian hormone (AMH) is produced by granulosa cells surrounding follicles that have undergone recruitment from the primordial follicle pool but have not been selected for dominance (preantral and early antral follicles). In healthy girls, serum levels of AMH vary considerably between individuals. We aimed to evaluate the AMH level in girls with premature thelarche (PT) and central precocious puberty (CPP). METHODS: Girls with CPP (n=21), PT (n=24) and a control prepubertal group (n=22) were included in the study. RESULTS: AMH levels were significantly higher in the PT group than the prepubertal control group and similar to the CPP group. AMH levels in the CPP group were similar to the prepubertal control group. AMH levels showed a significant negative correlation with luteinizing hormone (LH), free testosterone and dehydroepiandrosterone sulphate (DHEAS) levels in the PT group. AMH levels were negatively correlated with height standard deviation score (HSDS), body mass index (BMI) SDS values and positively correlated with sex hormone binding globulin (SHBG) levels in the CPP group. These levels were positively correlated with SHBG levels in the control prepubertal group. CONCLUSIONS: Serum AMH levels in girls with PT was found to be higher than in prepubertal girls. AMH levels in the CPP group were not different compared with the PT and control groups.
Assuntos
Hormônio Antimülleriano/sangue , Biomarcadores/sangue , Puberdade Precoce/sangue , Estudos de Casos e Controles , Criança , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Seguimentos , Humanos , Hormônio Luteinizante/sangue , Prognóstico , Puberdade Precoce/diagnóstico , Testosterona/sangueRESUMO
The Miller-McKusick-Malvaux (3M) syndrome is a rare autosomal disorder that can lead to short stature, dysmorphic features, and skeletal abnormalities with normal intelligence. A 16-month-old female patient had been referred to our clinic due to short stature. Case history revealed a birth weight of 1740 grams on the 39th week of gestation, with a birth length of 42 cm and no prior hereditary conditions of clinical significance in her family. On physical examination, her length was 67 cm [-3.6 standard deviation (SD) score], weight 7.2 kg (-2.9 SD score), and head circumference 42 cm (below 3rd percentile). She also had numerous characteristic physical features such as a triangular face, fleshy nose tip, a long philtrum, prominent mouth and lips, pointed chin, lumbar lordosis, and prominent heels. As her growth retardation had a prenatal onset and the physical examination results were suggestive of a characteristic profile, the diagnosis of 3M syndrome was strongly considered. Genetic assessment of the patient revealed a novel homozygous p.T425Nfs*40 [corrected] mutation in the OBSL1 gene. It is recommended that physicians pay further attention to this condition in the differential diagnosis of children with severe short stature.