RESUMO
BACKGROUND: Childhood obesity leads to many complications including impaired respiratory function. There are various anthropometric parameters related to obesity. OBJECTIVE: To investigate the correlation between anthropometric indices and pulmonary function test results in children without asthma. METHODS: Children without any respiratory disorders were enrolled in this study. Anthropometric measurements, such as height, weight, neck circumference (NC), and waist circumference, were obtained from the enrollees and body mass index was calculated. Afterward, pulmonary function tests were performed using spirometry. RESULTS: A total of 178 children (106 boys, 59.5%) with a mean age of 9.7 years were included the study. NC was above the 90th percentile in 65 children. Importantly, pulmonary parameters, such as forced expiratory volume during the first second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC), were lower in subjects with a large NC. Similarly, waist circumference was above the 90th percentile in 67 children, and FEV1/FVC was significantly lower in children with a large waist circumference. Moreover, there was a statistically significant negative correlation among FEV1, FEV1/FVC, and body mass index SD score. Also, multivariable linear regression analysis showed that an NC above the 90th percentile was associated with lower FEV1 and FEV1/FVC values. CONCLUSION: We identified NC as a novel anthropometric index that is strongly correlated with respiratory functions in children. Therefore, close monitoring of respiratory symptoms, particularly in children with obesity and a large NC, could help with early and prompt determination of respiratory complications of obesity.
Assuntos
Pesos e Medidas Corporais , Pulmão/fisiologia , Pescoço/anatomia & histologia , Adolescente , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Obesidade/epidemiologia , Testes de Função RespiratóriaRESUMO
BACKGROUND: Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess the management characteristics in DiN compared with developed nations [DeN]. METHODS: A questionnaire was sent between April 2010 and May 2011 to 87 members of the International Pediatric Nephrology Association, in 50 countries. RESULTS: A total of 213 patients were included from 41 centres in 30 nations (109 from 17 DiN and 104 from 13 DeN). 7% of DiN patients died at a median age of 5 years whereas no death was observed in DeN. DiN patients were older at the time of diagnosis. In DiN, leukocyte cystine measurement was only available in selected cases for diagnosis but never for continuous monitoring. More patients had reached end-stage renal disease in DiN (53.2 vs. 37.9%, p = 0.03), within a shorter time of evolution (8 vs. 10 yrs., p = 0.0008). The earlier the cysteamine treatment, the better the renal outcome, since the median renal survival increased up to 16.1 [12.5-/] yrs. in patients from DeN treated before the age of 2.5 years of age (p = 0.0001). However, the renal survival was not statistically different between DeN and DiN when patients initiated cysteamine after 2.5 years of age. The number of transplantations and the time from onset of ESRD to transplantation were not different in DeN and DiN. More patients were kept under maintenance dialysis in DiN (26% vs.19%, p = 0.02); 79% of patients from DiN vs. 45% in DeN underwent peritoneal dialysis. CONCLUSIONS: Major discrepancies between DiN and DeN in the management of nephropathic cystinosis remain a current concern for many patients living in countries with limited financial resources.
Assuntos
Cistinose/epidemiologia , Saúde Global , Internacionalidade , Falência Renal Crônica/epidemiologia , Médicos , Inquéritos e Questionários , Adolescente , Adulto , Criança , Pré-Escolar , Cistinose/diagnóstico , Cistinose/terapia , Países em Desenvolvimento , Feminino , Seguimentos , Humanos , Lactente , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Obesity is a well-established risk factor for asthma. Previous studies have reported that central obesity is associated with asthma. OBJECTIVE: To investigate the association between fat distribution, which is determined by anthropometric measures, including neck circumference (NC), and asthma in school-aged children. METHODS: Children diagnosed as having asthma were enrolled along with controls who were admitted to our outpatient department with allergic symptoms, such as rhinitis, urticaria and atopic dermatitis. Anthropometric measures, including height, weight, NC, waist circumference, and hip circumference, were obtained. Skin prick tests, blood eosinophil counts, and serum total IgE level measurements were performed. RESULTS: A total of 196 children (92 male [46.9%]) were included. Asthma was present in 102 patients (52.1%). Ninety-one of the patients (46.4%) were overweight, and 45 patients (22.9%) were obese. The NC of children with asthma was significantly higher than that of children in the control group. Grades defined according to NC percentiles were also significantly different between groups. In children with asthma, the prevalence of children with an NC higher than the 90th percentile (grade 6) was more frequent when compared with controls. The median NC of obese-overweight children with asthma was significantly higher compared with obese-overweight controls without asthma. Results of multivariable logistic regression analysis revealed that the presence of an NC in the greater than 90th percentile was associated with asthma in obese-overweight children. CONCLUSION: This study found that NC, which is a simple anthropometric measure, is associated with asthma in obese children.
Assuntos
Asma/diagnóstico , Pescoço/anatomia & histologia , Obesidade/diagnóstico , Alérgenos/imunologia , Asma/sangue , Pesos e Medidas Corporais , Criança , Eosinófilos/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Obesidade/sangue , Testes CutâneosRESUMO
BACKGROUND: Obesity is an established risk factor for asthma in children. Measures of central obesity are reported to be more associated with the severity of asthma in adults. The aim of the study was to investigate the association between fat distribution, which is determined by anthropometric measures including neck circumference (NC) and asthma severity in children. METHODS: Children with asthma who were followed in our pediatric allergy unit were consecutively recruited. Asthma severity was graded according to GINA guidelines. Children whose asthma was controlled with Step 1 or 2 treatment options formed Group 1 (mild asthma), whereas children who needed Step 3, 4, or 5 treatment options formed Group 2 (moderate-to-severe asthma). Anthropometric measures including height, weight, NC, waist circumference, and hip circumference were obtained. RESULTS: A total of 127 children (82 male, 64.6%) with a median age of 8.3 (6.4-11.3) years were included. Atopy was present in 77 (60.6%) patients. 91 patients (71.6) were in the mild asthma group. NC of children with severe asthma was significantly wider than children with mild asthma (29.0 cm (27.0-32.0) vs. 28.0 (26.0-30.0), p = 0.019). The prevalence of children with NC higher than 90th percentile was also more frequent in children with severe asthma (15 [41.7%] vs. 21 [23.1%]). Result of multivariable logistic regression analysis revealed that presence of NC >90th percentile was associated with severe asthma in children (odds ratio; [95% confidence interval] (2.52 [1.05-6.01]; p = 0.038). CONCLUSIONS: Neck circumference, which is a simple anthropometric tool, is associated with asthma severity in children.
Assuntos
Adiposidade , Asma/etiologia , Pescoço/patologia , Obesidade Infantil/complicações , Fatores Etários , Antropometria , Asma/diagnóstico , Criança , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Obesidade Infantil/patologia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Patients with Albright hereditary osteodystrophy (AHO) phenotype are usually seen in pediatric endocrinology policlinics when they are evaluated for short stature and/or obesity. Brachydactyly mental retardation syndrome (BDMR, OMIM #600430) is a rare genetic disorder caused by aberrations of chromosomal region 2q37 and characterized with AHO-like phenotype without any hormone resistance. Diagnosis of BDMR is based on the detection of the deletion on the long arm of chromosome 2. Diagnosis can usually be made with karyotype analysis but sometimes chromosomal deletion can only be detected by fluorescent in situ hybridization (FISH) screening. We report a patient with the AHO phenotype whose karyotype was normal but who was diagnosed with BDMR with FISH analysis showing 2q deletion. In pediatric endocrinology practice, in patients with AHO phenotype but without parathormone (PTH) resistance, BDMR should be considered. For the diagnosis of BDMR, the subtelomeric region of chromosome 2 should be screened for deletion by FISH analysis even in patients with normal karyotypes.
Assuntos
Braquidactilia/genética , Deficiência Intelectual/genética , Pseudopseudo-Hipoparatireoidismo/diagnóstico , Criança , Diagnóstico Diferencial , Feminino , Humanos , Pseudopseudo-Hipoparatireoidismo/genéticaRESUMO
Causes of hyperglycemia in critically ill non-diabetic children may differ from those in adults. The objective of this study was to investigate the pathogenesis of critical illness hyperglycemia (CIH) in terms of insulin resistance and ß-cell dysfunction. Critically ill children with blood glucose (BG) levels of >150 mg/dL (8.3 mmol/L) were enrolled in the study. Insulin sensitivity and ß-cell function in the hyperglycemic and euglycemic periods were analyzed with BG/insulin and BG/C-peptide ratios, and utilizing homeostasis model assessment (HOMA). A total of 40 patients were enrolled in the study. BG/insulin and BG/C-peptide ratios were significantly higher in the hyperglycemic period. The HOMA-B and S scores for the hyperglycemic period revealed that out of all the patients who survived (n=30), 20 had ß-cell dysfunction, while the remaining (n=11) had insulin resistance. ß-cell dysfunction was significantly higher in the hyperglycemic period (p<0.001). As in adults, ß-cell dysfunction may play a major role in the pathophysiology of CIH in children.
Assuntos
Estado Terminal , Hiperglicemia/etiologia , Adolescente , Glicemia/análise , Peptídeo C/sangue , Criança , Pré-Escolar , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/fisiopatologia , Lactente , Resistência à Insulina , Células Secretoras de Insulina/fisiologia , MasculinoRESUMO
UNLABELLED: Clinical findings illustrate the wide spectrum of the phenotypic manifestations of 45,X/46,XY mosaicism in the sex chromosome disorders of sex differentiation (DSD). The objective of study is to evaluate the characteristics of 45,X/46,XY patients and questioning of their place within the DSD categorization. The clinical findings of 11 patients with 45,X/46,XY mosaicism are described including the presentation, gonadal morphology, genital anatomy, and the hormone levels among 285 patients with DSD evaluated. Sixty-seven patients were diagnosed with sex chromosome DSD (50 Turner, three Klinefelter, ten 45,X/46,XY gonadal disgenesis, one 45X/46,XY ovotesticular DSD, one 47,XYY ovotesticular DSD, and two 46,XX/46,XY ovotesticular DSD). The type and the percentage of patients with 45,X/46,XY mosaicism were as follows: Four cases of mix gonadal dysgenesis, four cases of partial gonadal dysgenesis, two cases of complete gonadal dysgenesis, one case of ovotesticular DSD. On the other hand, another patient that has 45,X/46,XX mosaicism was diagnosed with MGD with the presence of the streak gonad on the right side and the testis on the other side. CONCLUSION: We suggest that sex chromosome DSD categorization can include 45,X/46,XY PGD and 45,X/46,XY CGD. Mixed gonadal dysgenesis may be also placed among the disorders of testicular differentiation of 46,XY DSD subdivision.
Assuntos
Heterogeneidade Genética , Disgenesia Gonadal Mista/classificação , Hormônios Esteroides Gonadais/sangue , Mosaicismo/classificação , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/classificação , Adolescente , Criança , Pré-Escolar , Feminino , Genitália/anormalidades , Disgenesia Gonadal Mista/genética , Humanos , Lactente , Recém-Nascido , Cariótipo , Masculino , Fenótipo , Estudos Retrospectivos , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , TurquiaRESUMO
The role of ACE gene insertion (I) or deletion (D) polymorphism on blood pressure phenotype is not clear in children. The aim of this work is to examine the association between hypertension and ACE I/D polymorphism, as well as the contribution of clinical and metabolic parameters on blood pressure. The study participants were 199 obese children. Forty-four of them were hypertensive. The hypertensive subjects were older than the normotensive and most of them were pubertal. The prevalence of hypertension in obese subjects with II, ID, and DD genotype was similar. There was no difference between the hypertensive and the normotensive group according to ACE I/D genotype, BMISDS, sex, blood glucose level and total cholesterol levels. In obese children, high IR-HOMA values, puberty, presence of family history for hypertension, hypertriglyceridemia, and low HDL-cholesterol, high triglyceride/HDL-cholesterol ratio were found as increased risk factors of hypertension. In obese children and adolescents, blood pressure did not differ by ACE I/D genotype. The presence of family history, puberty, insulin resistance and hypertriglyceridemia constitute important risk factors for developing hypertension.
Assuntos
Hipertensão/etiologia , Hipertensão/genética , Hipertensão/metabolismo , Obesidade/complicações , Adolescente , Idade de Início , Índice de Massa Corporal , Criança , Pré-Escolar , Suscetibilidade a Doenças/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Hipertensão/epidemiologia , Lactente , Resistência à Insulina/fisiologia , Masculino , Obesidade/epidemiologia , Obesidade/genética , Obesidade/metabolismo , Prevalência , Fatores de RiscoRESUMO
Intracranial cysts (ICC) may cause a wide spectrum of endocrinological disorders. We evaluated 27 patients who were diagnosed with ICC during investigation for neuroendocrine dysfunctions and reviewed the relevant literature. The types of ICC in the patients were arachnoid cysts (n = 13); Rathke cleft cysts (n = 7); pineal cysts (n = 5); an ependymal cyst (n = 1) and a cavum septum pellucidum cyst (n = 1). The neuroendocrine dysfunctions of the patients were obesity (n = 7), isolated growth hormone deficiency (n = 6), central precocious puberty (n = 6), multiple pituitary hormone deficiency (n = 3), central diabetes insipidus (n = 1), growth hormone deficiency and central precocious puberty (n = 1), obesity and galactorrhea (n = 1), obesity and hypogonadotropic hypogonadism (n = 1) and growth hormone neurosecretory dysfunction (n = 1). Only three patients, who had arachnoid cysts, showed neurologic symptomatology. Although three patients underwent surgery, no improvements in endocrinological dysfunctions were observed. ICC should be considered when evaluating patients with endocrinological problems and patients with coincidental ICC should be recommended for follow-up.
Assuntos
Cistos Aracnóideos/diagnóstico , Cistos do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Endócrino/diagnóstico , Cistos Aracnóideos/fisiopatologia , Cistos do Sistema Nervoso Central/fisiopatologia , Criança , Diagnóstico por Imagem , Doenças do Sistema Endócrino/fisiopatologia , Epêndima/patologia , Humanos , Glândula Pineal/patologia , Septo Pelúcido/patologiaRESUMO
High rates of skeletal complications, growth disturbances, thyroid and gonadal dysfunction have been described in children undergoing stem cell transplantation. Although secondary adrenal insufficiency has been diagnosed, no primary adrenal insufficiency has been reported after busulfan and cyclophosphamide (Bu/Cy)-based conditioning regimens for stem cell transplantation in children. A 9-year-old girl with myelodysplastic syndrome was treated with stem cell transplantation of allogeneic origin. She received myeloablative conditioning chemotherapy, Bu and Cy. Her serum cortisol level was normal before stem cell transplantation. Then, 17 months after stem cell transplantation, chronic graft-versus-host disease developed and was treated with methyl prednisolone for 3 months. The control endocrinological investigation revealed low serum cortisol and high serum adrenocorticotropin (ACTH) levels 6 months after completion of methyl prednisolone treatment. The ACTH stimulation test demonstrated primary adrenal insufficiency, and the other etiologies of primary adrenal insufficiency were excluded. The patient received oral prednisolone replacement therapy. She was followed-up for 44 months and required increases in steroid doses during stress periods. Primary adrenal insufficiency which was observed in our patient after Bu/Cy-based conditioning regimen for stem cell transplantation has not been reported in children and adrenal function should be closely monitored in these patients both before stem cell transplantation and after stem cell transplantation.
Assuntos
Doença de Addison/induzido quimicamente , Bussulfano/efeitos adversos , Ciclofosfamida/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/efeitos adversos , Criança , Feminino , Humanos , Agonistas Mieloablativos/efeitos adversosRESUMO
We aimed to determine the prevalence and clinical characteristics of non-classical congenital adrenal hyperplasia (NCCAH) with V281L mutation in patients with premature pubarche. An adrenocorticotrophic hormone (ACTH) stimulation test was performed in 14 of the 159 patients with premature pubarche (PP). Patients whose stimulated 17alpha-hydroxyprogesterone (17-OHP) level on the ACTH test was > or =10 ng/mL underwent a mutational analysis of the CYP21 gene. NCCAH was defined in nine (5.7%) patients, all of whom had the V281L mutation. Four of the NCCAH patients were homozygote and four of them were heterozygote. One other patient was compound heterozygote for V281L mutation and the I2 splice mutation. One of the patients with V281L heterozygous mutation developed true precocious puberty and the other one had rapid progressive early puberty and developed polycystic ovary syndrome. ACTH stimulated 17-OHP > or = 10 ng/mL in PP patients is load star to mutation analysis and heterozygote patients should be followed for clinical and biological hyperandrogenism up to completion of the whole 'genome sequence'.
Assuntos
Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/genética , Mutação Puntual , Puberdade Precoce/epidemiologia , Puberdade Precoce/genética , Esteroide 21-Hidroxilase/genética , Hiperplasia Suprarrenal Congênita/fisiopatologia , Criança , Pré-Escolar , Feminino , Heterozigoto , Homozigoto , Humanos , Masculino , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/genética , PrevalênciaRESUMO
BACKGROUND: Recessive mutations in ABCC8/KCNJ11 of beta-cell K(ATP) channel generally cause severe medically unresponsive hyperinsulinemic hypoglycemia (HH). Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. To date the phenotype of patients with dominant mutations seems to be different from those with recessive mutations as the majority of patients are responsive to diazoxide therapy. Controversy exists on whether these dominant ABCC8 or KCNJ11 genes mutations predispose to diabetes mellitus in adulthood or not. SUBJECTS: We report the clinical and genetic characteristics of five patients with neonatal HH, three had recessively inherited K(ATP) channel mutations and two with a dominantly acting mutation. As a result of failure to medical therapy, patients with recessive K(ATP) channel mutations underwent a near total pancreatectomy. Two siblings with a novel dominant mutation showed good response to medical treatment. Although the HH remitted in early infancy, they became diabetic at the prepubertal age. Their mother, maternal aunt and maternal grandfather had the same mutation without any medical history of neonatal HH. CONCLUSION: The clinical presentation of our two patients with a dominant ABCC8 mutation was milder than that of patients with the resessive form of the disease as they responded well to medical management.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Hiperinsulinismo Congênito/genética , Células Secretoras de Insulina/fisiologia , Canais de Potássio Corretores do Fluxo de Internalização/genética , Receptores de Droga/genética , Adolescente , Peso ao Nascer/genética , Criança , Pré-Escolar , Hiperinsulinismo Congênito/fisiopatologia , Hiperinsulinismo Congênito/terapia , Feminino , Genes Dominantes , Genes Recessivos , Humanos , Canais KATP/genética , Masculino , Linhagem , Receptores de Sulfonilureias , Resultado do TratamentoRESUMO
Neonatal diabetes mellitus (NDM) is a rare condition that can be either transient or permanent. K(ATP) channel (Kir6.2 or SUR1) mutation, chromosome 6 abnormalities, insulin, or glucokinase gene mutations can lead to isolated NDM. Cases caused by Kir6.2 mutation usually result in permanent NDM (PNDM) rather than transient NDM (TNDM). The majority of patients with the Kir6.2 or SUR1 mutation can be successfully managed with a sulfonylurea agent, without the need for insulin. We report a preterm male with NDM having two novel missense mutations, E322A and D352H, in the KCNJ11 gene. At 2 months of age, successful transition from insulin to glibenclamide (glyburide) therapy of the patient was managed. At 5 months of age, his diabetes went in to remission.
Assuntos
Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Glibureto/uso terapêutico , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Humanos , Hipoglicemiantes/uso terapêutico , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Insulina Glargina , Insulina de Ação Prolongada/uso terapêutico , Masculino , Mutação Puntual/genética , Indução de RemissãoRESUMO
We aimed in this study to investigate carotid intima-media thickness (IMT) in obese children and evaluate the relationship of IMT to various cardiovascular risk factors. One-hundred four obese children (9.3 +/- 2.5 years) and 30 healthy age-matched control subjects were enrolled in the study. All children were assessed for fasting levels of glucose, insulin, lipid profile, skinfold thickness (SFT), waist circumference (WC), and blood pressure (BP). Insulin resistance was estimated by the homeostasis model assessment (HOMA) index. Carotid IMT measurements and non-alcoholic fatty liver disease (NAFLD) were diagnosed with ultrasonographic findings. IMT was significantly higher in obese children compared to controls (0.49 +/- 0.05 vs. 0.40 +/- 0.02 mm, p < 0.001). Significant positive correlations were found between increased carotid IMT and body fat percentage (BFP), body mass index (BMI), age, height, systolic BP, WC, SFT, triglyceride and insulin levels, and insulin resistance index. In a linear logistic regression analysis, the only parameter affecting the increase in carotid IMT was WC (beta: 0.589, p < 0.001). Furthermore, IMT was increased significantly in obese children with NAFLD when compared to obese children without NAFLD (0.54 +/- 0.04 vs. 0.48 +/- 0.05 mm, p < 0.001). Children with abdominal obesity are at increased risk for atherosclerosis, and WC can be used to determine the atherosclerosis risk in obese children.
Assuntos
Artéria Carótida Primitiva/patologia , Obesidade Abdominal/epidemiologia , Artéria Carótida Primitiva/diagnóstico por imagem , Criança , Comorbidade , Dislipidemias/epidemiologia , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Masculino , Hepatopatia Gordurosa não Alcoólica , Fatores de Risco , Túnica Íntima/patologia , Túnica Média/patologia , UltrassonografiaRESUMO
The two well-described osteolysis syndromes associated with matrix metalloproteinase-2 deficiency and mutations in the metalloproteinase-2 gene are Torg-Winchester syndrome and nodulosis-arthropathy-osteolysis variant. They are characterized by carpal-tarsal destruction, subcutaneous nodules, and generalized osteoporosis and show autosomal recessive inheritance. Herein, we report two siblings affected with a novel mutation in matrix metalloproteinase 2 gene and discuss their clinical and radiographic findings.
Assuntos
Metaloproteinase 2 da Matriz/genética , Osteólise/genética , Adolescente , Criança , Humanos , Artropatias/diagnóstico por imagem , Artropatias/genética , Masculino , Metaloproteinase 2 da Matriz/deficiência , Mutação , Osteólise/diagnóstico por imagem , Papiledema/genética , RadiografiaRESUMO
Molecular genetic characterization of mutations in SRD5A2 gene is used as an essential procedure for the final diagnosis of 5alpha-reductase deficiency. Here, we report a novel homozygous point mutation of SRD5A2 gene at codon 65 in exon 1, due to a proline for alanine substitution in a Turkish family whose proband has severe undervirilization. This mutation has not been reported up to date in association with 5alpha-reductase deficiency in various ethnic groups. We discussed some questions about gender assignment in addition to the molecular and clinical characteristics of the disease.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/deficiência , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Identidade de Gênero , Mutação Puntual , Caracteres Sexuais , Alanina , Criança , Códon/genética , Éxons/genética , Família , Feminino , Homozigoto , Humanos , Prolina , TurquiaRESUMO
BACKGROUND/OBJECTIVE: The identification of the different subtypes of amiodarone-induced thyrotoxicosis (AIT) may provide a rational basis for the choice of the appropriate medical treatment. The aim of this study was to evaluate differential diagnosis and treatment regimens of AIT in children and adolescent. PATIENTS: We reported 3 patients: A 6.7 years old boy with type I AIT; a 17.9 years old girl with type II AIT and a 14.6 years old girl with mixed type AIT. CONCLUSIONS: AIT is not an uncommon complication in countries with low iodine intake. AIT can be asymptomatic and can occur at any time in patients receiving amiodarone therapy. It is also very important to distinguish the type of AIT when planning therapy. Steroid therapy should be started when findings indicate type II or mixed-type AIT. Beta blockers may prevent heart thyrotoxicosis and recurrence of primary arrhythmia if amiodarone is discontinued.
Assuntos
Amiodarona/efeitos adversos , Tireotoxicose/induzido quimicamente , Adolescente , Antiarrítmicos/efeitos adversos , Criança , Feminino , Humanos , Masculino , Tireotoxicose/sangue , Tireotoxicose/diagnóstico , Tiroxina/sangue , Resultado do Tratamento , Tri-Iodotironina/sangueRESUMO
Insulin receptor (INSR) mutations lead to heterogeneous disorders that may be as severe as Donohue syndrome or as mild as "type A insulin resistance syndrome". Patients with severe disorders usually harbor homozygous or compound heterozygous mutations. In contrast, type A insulin resistance syndrome has been associated with heterozygous mutations; homozygous mutations are rarely responsible for this condition. We report a novel, homozygous mutation, p.Leu260Arg in exon 3, of the INSR gene in a female adolescent patient with type A insulin resistance syndrome together with clinical details of her medical follow-up. Different mutations in the INSR gene cause different phenotype and vary depending on the inheritance pattern. This report adds to the literature, increases understanding of the disease mechanism and aids in genetic counseling.
RESUMO
Objective: Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disorder caused by mutations in the 1α-hydroxylase gene (CYB27B1). As it may be confused with nutritional rickets and hypophosphatemic rickets, genetic analysis is important for making a correct diagnosis. Methods: We analysed genomic DNA from 11 patients from eight different Turkish families. The patients were recruited for our studies if they presented with a diagnosis of VDDR. Results: The mean ± standard deviation age at diagnosis was 13.1±7.4 months. Seven patients had mild hypocalcemia at presentation while four patients had normal calcium concentrations. All patients underwent CYP27B1 gene analysis. The most prevalent mutation was the c.195 + 2T>G splice donor site mutation, affecting five out of 11 patients with VDDR1A. Two patients from the fourth family were compound heterozygous for c.195 + 2T>G and c.195 + 2 T>A in intron-1. Two patients, from different families, were homozygous for a previously reported duplication mutation in exon 8 (1319_1325dupCCCACCC, Phe443Profs*24). One patient had a homozygous splice site mutation in intron 7 (c.1215 + 2 T>A) and one patient had a homozygous mutation in exon 9 (c.1474 C>T). Conclusion: Intron-1 mutation was the most common mutation, as previously reported. All patients carrying that mutation were from same city of origin suggesting a "founder" or a "common ancestor" effect. VDDR1A should definitely be considered when a patient with signs of rickets has a normal 25-OHD level or when there is unresponsiveness to vitamin D treatment.
Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Raquitismo Hipofosfatêmico Familiar/genética , Análise de Sequência de DNA , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Linhagem , TurquiaRESUMO
Hypophosphatasia (HPP) is a rare disease caused by mutations in the ALPL gene encoding tissue-non-specific isoenzyme of alkaline phosphatase (TNSALP). Duplications of the ALPL gene account for fewer than 1% of the mutations causing HPP. It has been shown that asfotase alfa enzyme replacement treatment (ERT) mineralizes the skeleton and improves respiratory function and survival in severe forms of HPP. Our patient was a newborn infant evaluated for respiratory failure and generalized hypotonia after birth. Diagnosis of HPP was based on low-serum ALP activity, high concentrations of substrates of the TNSALP and radiologic findings. On day 21 after birth, ERT using asfotase alfa (2 mg/kg three times per week, subcutaneous injection) was started. His respiratory support was gradually reduced and skeletal mineralization improved during treatment. We were able to discharge the patient when he was seven months old. No mutation was detected in the ALPL gene by all exon sequencing, and additional analysis was done by quantitative polymerase chain reaction (qPCR). As a result, a novel homozygote duplication encompassing exons 2 to 6 was detected. Early diagnosis and rapid intervention with ERT is life-saving in the severe form of HPP. qPCR can detect duplications if a mutation cannot be detected by sequence analysis in these patients.