COMPLEXITY OF PEDIATRIC CHRONIC DISEASE: CROSS-SECTIONAL STUDY WITH 16,237 PATIENTS FOLLOWED BY MULTIPLE MEDICAL SPECIALTIES.

OBJECTIVE: To assess demographic data and characteristics of children and adolescents with pediatric chronic diseases (PCD), according to the number of specialties/patient. METHODS: We performed a cross-sectional study with 16,237 PCD patients at outpatient clinics in one year. Data were analyzed by an electronic data system, according to the number of physician appointments for PCD. This study assessed: demographic data, follow-up characteristics, types of medical specialty, diagnosis (International Statistical Classification of Diseases and Related Health Problems - ICD-10), number of day hospital clinic visits, and acute complications. RESULTS: Patients followed by ≥3 specialties simultaneously showed a significantly higher duration of follow-up compared to those followed by ≤2 specialties [2.1 (0.4-16.4) vs. 1.4 (0.1-16.2) years; p<0.001] and a higher number of appointments in all specialties. The most prevalent medical areas in patients followed by ≥3 specialties were: Psychiatry (Odds Ratio - OR=8.0; confidence interval of 95% - 95%CI 6-10.7; p<0.001), Palliative/Pain Care (OR=7.4; 95%CI 5.7-9.7; p<0.001), Infectious Disease (OR=7.0; 95%CI 6.4-7.8; p<0.001) and Nutrology (OR=6.9; 95%CI 5.6-8.4; p<0.001). Logistic regressions demonstrated that PCD patients followed by ≥3 specialties were associated with high risk for: number of appointments/patient (OR=9.2; 95%CI 8.0-10.5; p<0.001), day hospital clinic visits (OR=4.8; 95%CI 3.8-5.9; p<0.001), emergency department visits (OR=3.2; 95%CI 2.9-3.5; p<0.001), hospitalizations (OR=3.0; 95%CI 2.7-3.3; p<0.001), intensive care admissions (OR=2.5; 95%CI 2.1-3.0; p<0.001), and deaths (OR=2.8; 95%CI 1.9-4.0; p<0.001). The diagnosis of asthma, obesity, chronic pain, and transplant was significantly higher in patients followed by ≥3 specialties. CONCLUSIONS: The present study showed that PCD patients who required simultaneous care from multiple medical specialties had complex and severe diseases, with specific diagnoses.

Complexity of pediatric chronic disease: cross-sectional study with 16,237 patients followed by multiple medical specialties / Complexidade da doença crônica pediátrica: estudo tranversal com 16.237 pacientes seguidos por múltiplas especialidades médicas

ABSTRACT Objective: To assess demographic data and characteristics of children and adolescents with pediatric chronic diseases (PCD), according to the number of specialties/patient. Methods: We performed a cross-sectional study with 16,237 PCD patients at outpatient clinics in one year. Data were analyzed by an electronic data system, according to the number of physician appointments for PCD. This study assessed: demographic data, follow-up characteristics, types of medical specialty, diagnosis (International Statistical Classification of Diseases and Related Health Problems - ICD-10), number of day hospital clinic visits, and acute complications. Results: Patients followed by ≥3 specialties simultaneously showed a significantly higher duration of follow-up compared to those followed by ≤2 specialties [2.1 (0.4-16.4) vs. 1.4 (0.1-16.2) years; p<0.001] and a higher number of appointments in all specialties. The most prevalent medical areas in patients followed by ≥3 specialties were: Psychiatry (Odds Ratio - OR=8.0; confidence interval of 95% - 95%CI 6-10.7; p<0.001), Palliative/Pain Care (OR=7.4; 95%CI 5.7-9.7; p<0.001), Infectious Disease (OR=7.0; 95%CI 6.4-7.8; p<0.001) and Nutrology (OR=6.9; 95%CI 5.6-8.4; p<0.001). Logistic regressions demonstrated that PCD patients followed by ≥3 specialties were associated with high risk for: number of appointments/patient (OR=9.2; 95%CI 8.0-10.5; p<0.001), day hospital clinic visits (OR=4.8; 95%CI 3.8-5.9; p<0.001), emergency department visits (OR=3.2; 95%CI 2.9-3.5; p<0.001), hospitalizations (OR=3.0; 95%CI 2.7-3.3; p<0.001), intensive care admissions (OR=2.5; 95%CI 2.1-3.0; p<0.001), and deaths (OR=2.8; 95%CI 1.9-4.0; p<0.001). The diagnosis of asthma, obesity, chronic pain, and transplant was significantly higher in patients followed by ≥3 specialties. Conclusions: The present study showed that PCD patients who required simultaneous care from multiple medical specialties had complex and severe diseases, with specific diagnoses.

RESUMO Objetivo: Avaliar dados demográficos e características de crianças e adolescentes com doenças crônicas pediátricas, de acordo com o número de especialidades/paciente. Métodos: Realizou-se um estudo transversal com 16.237 pacientes com doenças crônicas pediátricas durante um ano. A análise foi feita em um sistema eletrônico, de acordo com número de consultas médicas para doenças crônicas pediátricas. Este estudo avaliou dados demográficos, características do seguimento, tipos de especialidades médicas, diagnóstico (10ª Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados com a Saúde - CID-10), número de visitas e complicações agudas. Resultados: Os pacientes acompanhados por três ou mais especialidades simultaneamente tiveram seguimento de maior duração comparados com aqueles seguidos por ≤2 especialidades [2,1 (0,4-16,4) vs. 1,4 (0,1-16,2) anos; p<0,001], bem como maior número de consultas em todas as especialidades. As áreas médicas mais comuns em pacientes acompanhados por ≥3 especialidades foram: psiquiatria (Odds Ratio - OR=8,0; intervalo de confiança de 95% - IC95% 6-10,7; p<0,001); dor/cuidados paliativos (OR=7,4; IC95% 5,7-9,7; p<0,001); doenças infecciosas (OR=7,0; IC95% 6,4-7,8; p<0,001); nutrologia (OR=6,9; IC95% 5,6-8,4; p<0,001). As regressões logísticas mostraram que os pacientes com doenças crônicas pediátricas seguidos por ≥3 especialidades tinham alto risco para: maior número de consultas/paciente (OR=9,2; IC95% 8,0-10,5; p<0,001); atendimentos em hospital-dia (OR=4,8; 95%IC3,8-5,9; p<0,001); atendimentos em pronto-socorro (OR=3,2; IC95% 2,9-3,5; p<0,001); hospitalizações (OR=3,0; IC95%2,7-3,3; p<0,001); internação em terapia intensiva (OR=2,5; IC95% 2,1-3,0; p<0,001); óbitos (OR=2,8; IC95%1,9-4,0; p<0,001). Os diagnósticos de asma, obesidade, dor crônica, transplante e infecção do trato urinário foram mais frequentes nos pacientes seguidos por três ou mais especialidades. Conclusões: O presente estudo mostrou que pacientes com doenças crônicas pediátricas que necessitaram de múltiplas especialidades médicas simultaneamente apresentavam doenças complexas e graves, com diagnósticos específicos.

Pitfalls in the diagnosis of insulin autoimmune syndrome (Hirata's disease) in a hypoglycemic child: a case report and review of the literature.

Background Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinemic hypoglycemia (HH) not addressed as a potential differential diagnosis in current pediatric guidelines. We present a case of IAS in a child with no previous history of autoimmune disease, no previous intake of triggering medications and absence of genetic predisposition. Case presentation A 6-year-old boy presented with recurrent HH (blood glucose of 26 mg/dL [1.4 mmol/L] and insulin of 686 µU/mL). Abdominal imaging was normal. After multiple therapeutic failures, we hypothesized misuse of exogenous insulin and factitious hypoglycemia. Council of Guardianship had the child separated from his mother, but insulin levels remained high. A chromatography test was then performed which showed high titers of endogenous insulin autoantibody (IAA) with early dissociation from the insulin molecule. The human leukocyte antigen (HLA) test showed a DRB1 *13:01/*08:02 genotype. The patient was advised to control food intake and physical activity routines. During a 5-year follow-up, hypoglycemic episodes were sparse, despite high insulin levels. Conclusions Misdiagnosis of IAS with factitious hypoglycemia may happen if IAS is not considered as a differential diagnosis, leading to potential traumatic consequences. Further efforts should be made to increase awareness of IAS as a differential diagnosis of hypoglycemia and to include it in pediatric guidelines.

Translation and validation of Pediatric Quality of Life InventoryTM 3 0 Diabetes Module (PedsQLTM 3 0 Diabetes Module) in Brazil-Portuguese language / Tradução e validação do Pediatric Quality of Life InventoryTM 3 0 Diabetes Module (PedsQLTM 3 0 Diabetes Module) para a língua portuguesa do Brasil

Abstract Objective: The aim of the present study was to create a translated version of the Pediatric Quality of Life InventoryTM 3.0 Diabetes Module (PedsQLTM 3.0 Diabetes Module) in Brazilian Portuguese that was conceptually equivalent to the original American English version and to linguistically validate it in a Brazilian pediatric population with type 1 diabetes mellitus and their parents or caregivers. Methods: The instrument was translated, back-translated, and then administered to 83 children/adolescents (5-18 years) with type 1 diabetes mellitus and their family members and to 25 parents/caregivers of patients aged between 2 and 4 years. The final translated version was tested for reliability by analyzing internal consistency, intraobserver (test-retest) reliability, and concurrent validity. Results: Cronbach's alpha coefficient for the total score of the questionnaires of children/adolescents (α = 0.85) and their parents (α = 0.82) was above the recommended minimum of 0.70 for group comparisons. Intraobserver reliability and concurrent validity exhibited a significant positive correlation (p < 0.001), indicating the reliability of the translated instrument. A moderate but significant positive correlation (r = 0.40; p < 0.001) was demonstrated between the total scores of patient self-report and parent proxy-report scales. There was no significant correlation between glycated hemoglobin (HbA1c) levels and the respective scores in the questionnaires answered by patients and their parents/caregivers. Conclusion: The analysis of the translated version of the PedsQLTM 3.0 Diabetes Module revealed adequate psychometric characteristics with respect to reliability and validity following administration to a sample of Brazilian children/adolescents with type 1 diabetes mellitus and their caregivers.

Resumo Objetivo: Produzir uma versão do questionário Pediatric Quality of Life InventoryTM 3.0 Diabetes Module (PedsQLTM 3.0 Diabetes Module) para a língua portuguesa do Brasil, que fosse conceitualmente equivalente à versão original em inglês, e proceder à sua validação linguística numa população pediátrica brasileira portadora de diabetes mellitus tipo 1 (DM1) e seus pais ou cuidadores. Métodos: A tradução do instrumento foi feita pela metodologia de tradução-tradução reversa, foi aplicado a 83 crianças/adolescentes (5-18 anos) portadores de diabetes mellitus tipo 1 com seus parentes e a 25 pais/cuidadores de pacientes entre 2 e 4 anos de idade. A confiabilidade da versão traduzida foi avaliada pelas seguintes análises: consistência interna, confiabilidade teste-reteste e validade concorrente. Resultados: O coeficiente alfa de Cronbach para a pontuação total do questionário das crianças/adolescentes (α = 0,85) e seus pais (α = 0,82) excedeu o mínimo recomendado 0,70 para comparação entre grupos. Na confiabilidade intraobservador e validade concorrente observou-se correlação positiva e estatisticamente significativa (p < 0,001), indicou a fidedignidade do instrumento traduzido. Na comparação entre os escores totais obtidos por pais/cuidadores e crianças/adolescentes, houve uma correlação positiva, pequena, mas significativa (r = 0,40; p < 0,001). Não houve correlações estatisticamente significativas entre os níveis de hemoglobina glicada e os escores obtidos nos questionários respondidos pelos pacientes e seus pais/cuidadores. Conclusão: As análises do instrumento PedsQLTM 3.0 Módulo Diabetes demonstraram propriedades psicométricas adequadas em termos de confiabilidade e validade quando aplicado nessa amostra de crianças/adolescentes brasileiros portadores de DM tipo 1 e seus cuidadores.

Translation and validation of Pediatric Quality of Life Inventory™ 3.0 Diabetes Module (PedsQL™ 3.0 Diabetes Module) in Brazil-Portuguese language.

OBJECTIVE: The aim of the present study was to create a translated version of the Pediatric Quality of Life Inventory™ 3.0 Diabetes Module (PedsQL™ 3.0 Diabetes Module) in Brazilian Portuguese that was conceptually equivalent to the original American English version and to linguistically validate it in a Brazilian pediatric population with type 1 diabetes mellitus and their parents or caregivers. METHODS: The instrument was translated, back-translated, and then administered to 83 children/adolescents (5-18 years) with type 1 diabetes mellitus and their family members and to 25 parents/caregivers of patients aged between 2 and 4 years. The final translated version was tested for reliability by analyzing internal consistency, intraobserver (test-retest) reliability, and concurrent validity. RESULTS: Cronbach's alpha coefficient for the total score of the questionnaires of children/adolescents (α=0.85) and their parents (α=0.82) was above the recommended minimum of 0.70 for group comparisons. Intraobserver reliability and concurrent validity exhibited a significant positive correlation (p<0.001), indicating the reliability of the translated instrument. A moderate but significant positive correlation (r=0.40; p<0.001) was demonstrated between the total scores of patient self-report and parent proxy-report scales. There was no significant correlation between glycated hemoglobin (HbA1c) levels and the respective scores in the questionnaires answered by patients and their parents/caregivers. CONCLUSION: The analysis of the translated version of the PedsQL™ 3.0 Diabetes Module revealed adequate psychometric characteristics with respect to reliability and validity following administration to a sample of Brazilian children/adolescents with type 1 diabetes mellitus and their caregivers.

Translation and validation of diabetes self-management profile (DSMP) into Brazilian Portuguese language: first instrument to assess type 1 diabetes self-management in a pediatric population.

OBJECTIVE: To translate and validate the instrument Diabetes Self-Management Profile (DSMP)-Conventional and Flexible Regimens into Brazilian Portuguese language in order to evaluate the quality of diabetes self-management in children and adolescents with type 1 diabetes and their caregivers. METHODS: DSMP was submitted to forward and back translation method and validated in a group of type 1 diabetes youths between 6 and 18 years (n = 102), and their families. Analysis of DSMP internal consistency, intra and interobserver reliability and concurrent correlation with HbA1c were done. RESULTS: DSMP total scores demonstrated adequate internal consistency (Cronbach's α = 0.79), 3-month test-retest reliability (ρ = 0.53; p < 0.001), inter-interviewer agreement (ρ = 0.55; p < 0.001). DSMP total score was significantly correlated to HbA1c (ρ = -0.54, p < 0.001). CONCLUSION: DSMP-translated version is a reliable and valid tool to assess diabetes self-management.

Maturity-onset diabetes of the young (MODY) in Brazil: Establishment of a national registry and appraisal of available genetic and clinical data.

AIMS: Maturity-Onset Diabetes of the Young (MODY) comprises a heterogeneous group of monogenic forms of diabetes caused by mutations in at least 14 genes, but mostly by mutations in Glucokinase (GCK) and hepatocyte nuclear factor-1 homeobox A (HNF1A). This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. METHODS: 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report. RESULTS: 72 individuals had GCK mutations, 9 described in Brazilian individuals for the first time. One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals. Comparisons of GCK probands vs HNF1A: age 16±11 vs 35±20years; age at diagnosis 11±8 vs 21±7years; BMI 19±6 vs 25±6kg/m2; sulfonylurea users 5 vs 83%; insulin users 5 vs 17%; presence of arterial hypertension 0 vs. 33%, all p<0.05. No differences were observed in lipids and C-peptide. CONCLUSIONS: Most MODY cases in Brazil are due to GCK mutations. In agreement with other studied populations, novel mutations are common. Only 14% of patients with familial diabetes carry a HNF1A mutation. Diagnosis of other rare forms of MODY is still a challenge in Brazilian population, as well as adequate strategies to screen individuals for molecular diagnosis.

Health-related quality of life in patients with type 1 diabetes mellitus in the different geographical regions of Brazil: data from the Brazilian Type 1 Diabetes Study Group.

BACKGROUND: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities. METHODS: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected. RESULTS: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North-Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined. CONCLUSIONS: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Clinical and molecular data from 61 Brazilian cases of Congenital Hyperinsulinemic Hypoglycemia.

OBJECTIVE: To study the clinical and molecular characteristics of a sample of Brazilian patients with Congenital Hyperinsulinemic Hypoglycemia (CHH). METHODS: Electronic message was sent to members from Endocrinology Department- Brazilian Society of Pediatrics requesting clinical data for all cases of CHH. A whole blood sample from living patients was requested for DNA extraction followed by a search for mutations of the genes ABCC8, KCNJ11, GCK, GLUD1, HADH, SLC16A1 and HNF4A. RESULTS: Of the 61 patients evaluated, 36 (59%) were boys, and only 16 (26%) were born by normal delivery. Gestational age ranged from 32 to 41 weeks (mean = 37 weeks and 6 days). Birth weight ranged from 1590 to 5250 g (mean = 3430 g). Macrossomia occurred in 14 cases (28%). Age at diagnosis ranged from 1 to 1080 days (mean = 75 days). DNA for molecular analysis was obtained from 53 of the 61 patients. Molecular changes in the ABCC8 gene were detected in 15 (28%) of these 53 cases, and mutations in the KCNJ11 gene were detected in 6 (11%). Mutations in the GLUD1 gene were detected in 9 cases (17%) of the total series. Mutations of the GCK gene in heterozygosis were detected in 3 cases. No mutations were detected in the sequencing of genes HADH, SLC16A1 and HNF4A. CONCLUSION: The present study conducted in Brazil permitted the collaborative compilation of an important number of CHH cases and showed that the present clinical and molecular data are similar to those of published global series.

Tireoidite autoimune na criança e no adolescente / Autoimmune thyroiditis in children and adolescents

Objetivo: Revisão da literatura sobre a tireoidite de Hashimoto no universo das doenças autoimunes em crianças e adolescentes. Fontes: MEDLINE, utilizando os termos tireoidite, doença de Hashimoto, genética da autoimunidade tireoidiana. Resumo: Doenças tireoidianas autoimunes são doenças endócrinas frequentes da criança e do adolescente. Genes como antígeno humano leucocitário (HLA), antígeno-4 associado ao linfócito T citotóxico (CTLA-4), a proteína tirosina-fosfatase 22 (PTPN22) e os genes específicos da glândula tireoide, como o receptor do TSH (TSHR) e tireoglobulina (Tg) afetam a resposta imunológica da tireoide. A tireoidite autoimune pode apresentar funções tireoidianas desde eutireoidismo até hipotireoidismo evidente, além de um quadro inicial, transitório, de hipertireoidismo e tem sido associada a doenças autoimunes como diabetes, doenças reumáticas, doença celíaca. Função tiroidiana e associações com outras doenças autoimunes são destacados...

Efficacy of photographic educational materials for carbohydrate counting training of adolescents with diabetes mellitus / Eficacia de materiales educativos fotográficos para entrenar a adolescentes con diabetes mellitus con el conteo de carbohidratos

Background: Carbohydrate counting (CHC) is acknowledged by the American Diabetes Association (ADA) as an important tool. Objective: To assess the efficacy of photographic educational materials to train adolescents with DM to perform CHC. Subjects and methods: 76 adolescents were randomly divided into two groups of CHC orientation: by means of photographic materials (Photo) or by a list of foods (List). One month afterwards, the participants were contacted via telephone to answer questions on CHC to reinforce the training (Quiz). Two days after taking the quiz, required the participants to visit an experimental kitchen to observe food portions in natura and to respond to a questionnaire on the weights in grams or carbohydrate equivalents of these portions. Statistical significance was established at p < 0.05. Results: 54 adolescents completed the study (79.7% female), with 51.8% allocated to the Photo group and 48.1% to the List group. The mean age was 13.8 ± 2.0 years old, and the mean body mass index (BMI) was 21.0 ± 3.2 kg/m2. The participants had average of 7.9 ± 1.5 years of schooling, while their parents had 8.0 ± 3.8 years. The knowledge of CHC was similar in both groups before the intervention. After the intervention, the Photo group achieved a significantly higher hit difference on the CHC assessment test than the List group (Photo: 2.5 vs List: 1.0; p = 0.03). Conclusions: The photographic educational material was more effective in helping adolescents with DM understand and learn to perform carbohydrate counting (AU)

Antecedentes: El conteo de carbohidratos (CCH) es reconocido por la Asociación Americana de Diabetes (AAD) como una herramienta importante. Objetivo: Evaluar la eficacia de materiales educativos fotográficos en el entrenamiento de adolescentes con DM para realizar el CCH. Sujetos y Métodos: se distribuyó al azar a 76 adolescentes a dos grupos de orientación de CCH: mediante materiales fotográficos (Foto) o mediante listado de alimentos (Lista). Un mes después, se contactó a los participantes por teléfono para responder a preguntas sobre CCH para reforzar el entrenamiento (Encuesta). Dos días después de la encuesta, se pidió a los participantes que visitaran una cocina experimental para observar las porciones de los alimentos al natural y responder a un cuestionario sobre los pesos en gramos o equivalentes de carbohidratos de estas porciones. Se estableció la significación estadística en un valor de p < 0,05. Resultados: 54 adolescentes completaron el estudio (79,7 % mujeres), siendo el 51,8 % asignados al grupo Foto y el 48,1 % al grupo Lista. La edad promedio fue de 13,8 ± 2,0 años y el índice de masa corporal (IMC) promedio fue de 21,0 ± 3,2 kg/m2. Los participantes tenían un promedio de 7,9 ± 1,5 años de escolarización, y sus padres 8,0 ± 3,8 años. EL conocimiento en el CCH fue similar en ambos grupos antes de la intervención. Después de la misma, el grupo Foto consiguió una diferencia significativa en la tasa de aciertos en el test de evaluación del CCH con respecto al grupo Lista (Foto: 2,5 frente a Lista: 1.0; p = 0,03). Conclusiones: el material educativo fotográfico fue más eficaz a la hora de ayudar a los adolescentes con DM a comprender y aprender a realizar el conteo de hidratos de carbono (AU)

A novel glucokinase deletion (p.Lys32del) and five previously described mutations co-segregate with the phenotype of mild familial hyperglycaemia (MODY2) in Brazilian families.

Six Brazilian families with mild familial hyperglycaemia have been screened for glucokinase (GCK) mutations. All had mutations that co-segregated with the phenotype. One of the mutations, the deletion 96_98delAAG (p.Lys32del), had not been previously described, reinforcing the worldwide prevalence of GCK MODY and widespread existence of undetected new mutations.

Economic status and clinical care in young type 1 diabetes patients: a nationwide multicenter study in Brazil.

The aim of this study is to evaluate the influence of economic status on clinical care provided to Brazilian youths with type 1 diabetes in daily practice, according to the American Diabetes Association's guidelines. This was a cross-sectional, multicenter study conducted between 2008 and 2010 in 28 public clinics in Brazil. Data were obtained from 1,692 patients (55.3 % female, 56.4 % Caucasian), with a mean age of 13 years (range, 1-18), a mean age at diagnosis of 7.1 ± 4 years and diabetes duration of 5 ± 3.7 years. Overall, 75 % of the patients were of a low or very low economic status. HbA1c goals were reached by 23.2 %, LDL cholesterol by 57.9 %, systolic blood pressure by 83.9 % and diastolic blood pressure by 73.9 % of the patients. In total, 20.2 % of the patients were overweight and 9.2 % were obese. Patients from very low economic status were less likely to attend tertiary care level when compared with those from low, medium and high economic status, 64.2 % versus 75.5 % versus 78.3 % and 74.0 %; p < 0.001, respectively. The rate of annual screening for retinopathy, nephropathy and for foot alterations was 66.2, 69.7 and 62.7 %, respectively. Insulin dose, age, very low economic status, daily frequency of self-blood glucose monitoring and female gender were independently associated with poor glycemic control. Screening for diabetic complications and attaining glucose, lipid and blood pressure goals present a challenge for young Brazilian type 1 diabetes patients. The low economic status of the majority of our patients may represent a barrier to reaching these goals.

Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities.

MCT8 is a cellular transporter of thyroid hormones important in their action and metabolization. We report a male patient with the novel inactivating mutation 630insG in the coding region in exon 1 of MCT8. He was characterized clinically by severe neurologic impairment (initially with global hypotonia, later evolving with generalized hypertonia), normal growth during infancy, reduced weight gain, and absence of typical signs and symptoms of hypothyroidism, while the laboratory evaluation disclosed elevated T3, low total and free T4, and mildly elevated TSH serum levels. Treatment with levothyroxine improved thyroid hormone profile but was not able to alter the clinical picture of the patient. These data reinforce the concept that the role of MCT8 is tissue-dependent: while neurons are highly dependent on MCT8, bone tissue, adipose tissue, muscle, and liver are less dependent on MCT8 and, therefore, may suffer the consequences of the exposition to high serum T3 levels.

Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome.

Wolcott-Rallison syndrome (WRS, OMIM 226980) is a rare autosomal recessive disorder characterized by permanent neonatal diabetes mellitus, epiphyseal dysplasia, and other multisystemic clinical manifestations. We described two novel mutations in the EIF2AK3 gene in two consanguineous families with WRS from Brazil and Morocco. We have observed in case 1 a homozygous C > T replacement at base pair c.1192 at exon 7, generating a stop codon at position 398 (Gln398Stop). Both of his parents were found to be heterozygous for the mutation. We detected in both parents of case 2, a deceased Moroccan girl, a duplication of base pair c.851A at exon 5 (c.851dupA) leading to a frameshift and a stop codon at position 285 (p.Pro285AlafsX3). Both cases 1 and 2 had neonatal diabetes mellitus, multiple epiphyseal dysplasia, and growth delay, and presented episodes of acute hepatic dysfunction. Case 1 presented central hypothyroidism, developmental delay, and mild mental retardation. Case 2 presented a fatal episode of acute renal failure. The clinical phenotype associated with the syndrome can be variable, but a combination of infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, and hepatic and/or renal dysfunction is the mainstay of diagnosis.

Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities / Mutação nova do gene MCT8 em menino Brasileiro com resistência ao hormônio tireioidiano e neuropatia grave

O MCT8 é um transportador celular de hormônios tireoidianos, importante para sua ação e metabolização. Relatamos o caso de um menino com a nova mutação inativadora 630insG no éxon 1 do MCT8. O paciente caracterizou-se por grave comprometimento neurológico (inicialmente com hipotonia global, evoluindo com hipertonia generalizada), crescimento normal nos dois primeiros anos de vida, reduzido ganho ponderal e ausência dos sinais e sintomas típicos de hipotireoidismo. A sua avaliação sérica revelou elevação do T3, redução do T4 total e livre e TSH levemente aumentado. O tratamento com levotiroxina melhorou o perfil hormonal tireoidiano, mas não modificou o quadro clínico do paciente. Esses dados reforçam o conceito de que o papel do MCT8 é tecido-dependente: enquanto os neurônios são altamente dependentes do MCT8, o osso, o tecido adiposo, o músculo e o fígado são menos dependentes do MCT8 e, portanto, podem sofrer as consequências da exposição a níveis séricos elevados de T3.

MCT8 is a cellular transporter of thyroid hormones important in their action and metabolization. We report a male patient with the novel inactivating mutation 630insG in the coding region in exon 1 of MCT8. He was characterized clinically by severe neurologic impairment (initially with global hypotonia, later evolving with generalized hypertonia), normal growth during infancy, reduced weight gain, and absence of typical signs and symptoms of hypothyroidism, while the laboratory evaluation disclosed elevated T3, low total and free T4, and mildly elevated TSH serum levels. Treatment with levothyroxine improved thyroid hormone profile but was not able to alter the clinical picture of the patient. These data reinforce the concept that the role of MCT8 is tissue-dependent: while neurons are highly dependent on MCT8, bone tissue, adipose tissue, muscle, and liver are less dependent on MCT8 and, therefore, may suffer the consequences of the exposition to high serum T3 levels.

Congenital hyperinsulinism in Brazilian neonates: a study of histology, KATP channel genes, and proliferation of ß cells.

Congenital hyperinsulinism (CHI) is a rare pancreatic ß-cell disease of neonates, characterized by inappropriate insulin secretion with severe persistent hypoglycemia, with regard to which many questions remain to be answered, despite the important acquisition of its molecular mechanisms in the last decade. The aim of this study was to examine pancreatic histology, ß-cell proliferation (immunohistochemistry with double staining for Ki-67/insulin), and ß-cell adenosine triphosphate-sensitive potassium channels genes from 11 Brazilian patients with severe medically unresponsive CHI who underwent pancreatectomy. Pancreatic histology and ß-cell proliferation in CHI patients were compared to pancreatic samples from 19 age-matched controls. Ten cases were classified as diffuse form (D-CHI) and 1 as focal form (F-CHI). ß-cell nucleomegaly and abundant cytoplasm were absent in controls and were observed only in D-CHI patients. The Ki-67 labeling index (Ki-67-LI) was used to differentiate the adenomatous areas of the F-CHI case (10.15%) from the "loose cluster of islets" found in 2 D-CHI samples (2.29% and 2.43%) and 1 control (1.54%) sample. The Ki-67-LI was higher in the F-CHI adenomatous areas, but D-CHI patients also had significantly greater Ki-67-LI (mean value  =  2.41%) than age-matched controls (mean value  =  1.87%) (P  =  0.009). In this 1st genetic study of CHI patients in Brazil, no mutations or new polymorphisms were found in the 33-37 exons of the ABCC8 gene (SUR1) or in the entire exon of the KCNJ11 gene (Kir 6.2) in 4 of 4 patients evaluated. On the other hand, enhanced ß-cell proliferation seems to be a constant feature in CHI patients, both in diffuse and focal forms.

Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome.

OBJECTIVE: Wolfram syndrome (WS) is a rare, progressive, neurodegenerative disorder with an autosomal recessive pattern of inheritance. The gene for WS, WFS1, was identified on chromosome 4p16 and most WS patients carry mutations in this gene. However, some studies have provided evidence for genetic heterogeneity and the genotype-phenotype relationships are not clear. Our aim was to ascertain the spectrum of WFS1 mutations in Brazilian patients with WS and to examine the phenotype-genotype relationships in these patients. DESIGN AND METHODS: Clinical characterization and analyses of the WFS1 gene were performed in 27 Brazilian patients with WS from 19 families. RESULTS: We identified 15 different mutations in the WFS1 gene in 26 patients, among which nine are novel. All mutations occurred in exon 8, except for one missense mutation which was located in exon 5. Although we did not find any clear phenotype-genotype relationship in patients with mutations in exon 8, the homozygous missense mutation in exon 5 was associated with a mild phenotype: onset of diabetes mellitus and optic atrophy during adulthood with good metabolic control being achieved with low doses of sulfonylurea. CONCLUSIONS: Our data show that WFS1 is the major gene involved in WS in Brazilian patients and most mutations are concentrated in exon 8. Also, our study increases the spectrum of WFS1 mutations. Although no clear phenotype-genotype relationship was found for mutations in exon 8, a mild phenotype was associated with a homozygous missense mutation in exon 5.

Baixa estatura por insensibilidade ao hormônio de crescimento / Short stature caused by growth hormone insensitivity

Objetivo: crianças portadoras de baixa estatura apresentam um grande número de opções diagnósticas. Muitas vezes não se consegue estabelecer o diagnóstico preciso...

Introduction: Tasks for diagnosing short stature in children has been challenged by a broad array of pathways. Precise diagnosis has been often unconspicuous...

Análise dos ajustes insulinoterápicos realizados a partir de dois esquemas de monitorização domiciliar em pacientes com diabetes mellitus do tipo 1 / Frequency and insulin adjustments among patients with type 1 diabetes mellitus

Objetivos: Identificar a freqüência e magnitude nos ajustes das doses de insulina a partir de dois esquemas de monitorização domiciliar sangüíneo e urinário em pacientes com diabetes mellitus do tipo 1 e avaliar a efetividade dos ajustes no controle metabólico. Métodos: Amostra de 25 pacientes dividida em dois grupos. Os do Grupo A realizaram monitorização domiciliar da glicemia capilar e os do Grupo B, monitorização domiciliar da glicosúria, conforme esquemas preconizados. Estes esquemas possibilitaram construção de pefis e de ajustes insulinoterápicos. Resultados: Houve 204 possibilidades de ajustes no Grupo A e 87 no Grupo B. com relação às doses de insulina NPH matutina, no Grupo A foram implementados 95 (46,57 por cento) ajustes e no Grupo B 30 (34,48 por cento) (p=0,03715). Os ajustes nas doses de insulina regular feitas antes do jantar também foram maiores no Grupo A, 22 (10,84 por cento) do que no Grupo B, 3 (3,45 por cento) (p=0,02852). O Grupo A apresentou-se com melhor controle metabólico (HbA1c=10,17 por cento) quanto comparado ao Grupo B (HbA1c=12,31 por cento). Conclusões: A monitorização domiciliar da glicemia possibilitou maior número de ajustes, maior número de aplicações e melhor controle metabólico.