Non-balanced translocation between the short arms of chromosomes 8 and 6 associated with type 1 diabetes mellitus.

SUMMARY: We describe a rare case of a girl with an initial diagnostic hypothesis of chromosome 8 trisomy based on clinical findings and karyotyping, which identified a structural change in the short arm of chromosome 8 (46,XX,add(8)(p23)). At the age of 7, she developed type 1 diabetes mellitus and started insulin therapy with multiple daily doses, and then she started to use a continuous insulin infusion system (pump) at 10 years of age. At the age of 12, she underwent a molecular study that identified an unbalanced translocation between the short arms of chromosomes 6 and 8 - 46,XX,add(8)(p23).ish der(8)t(6;8)(GS-196I5+;RP-11338B22-). LEARNING POINTS: Patients with an unbalanced translocation between the short arms of chromosomes 6 and 8 - 46,XX,add(8)(p23).ish der(8)t(6;8)(GS-196I5+;RP-11338B22-) may present syndromic features suggestive of chromosome 8 trisomy. Main characteristics are a prominent forehead, ocular and breast hypertelorism, ocular, external ear and palate abnormalities, a short neck, heart defects, and developmental delay. Patients with 46,XX,add(8)(p23).ish der(8)t(6;8)(GS-196I5+;RP-11338B22-) may present autoimmune type 1 diabetes mellitus. Karyotyping is an essential tool for the diagnosis of chromosomal changes, but it has some limitations. Multiplex ligation-dependent probe amplification, array-single nucleotide polymorphism and fluorescence in situ hybridization can help diagnose genetic syndromes in patients with atypical evolution.

Evaluation of sleep characteristics of children and adolescents with type 1 diabetes mellitus / Avaliação das características do sono em crianças e adolescentes portadores de diabetes melito tipo 1

ABSTRACT Objective: To evaluate sleep characteristics of children and adolescents with type 1 diabetes mellitus (T1DM) and their relationship with glycemic control. Methods: A cross-sectional study was conducted at a public hospital in São Paulo, Brazil. It included 86 patients with T1DM, aged between 10 and 18 years old, who were on insulin therapy, had performed at least three measurements of capillary blood glucose throughout the day, and had normal thyroid function. The clinical, anthropometric, and laboratory data of each patient were evaluated. The Pediatric Daytime Sleepiness Scale (PDSS) and the Munich Chronotype Questionnaire (MCTQ) were used to assess the sleep characteristics. Results: The mean level of glycated hemoglobin (HbA1c) was 9.2±2.1%, and it was higher in adolescents than in children. The mean score of PDSS was 13.9±4.7. Patients with HbA1c<7.5% had lower PDSS scores and longer sleep duration on weekdays than patients with HbA1c≥7.5%. HbA1c levels were negatively correlated with chronotype values and sleep duration on weekdays and positively correlated with social jet lag. Patients who had had T1DM for less than three years had a higher prevalence of daytime sleepiness. The regression analysis showed that higher HbA1c (≥7.5%) and shorter time since the diagnosis of T1DM increased the chance of daytime sleepiness, regardless of age and sex. Conclusions: Patients with higher HbA1c had more daytime sleepiness, a morning chronotype, shorter sleep duration on weekdays and a more significant social jet lag. The shorter diagnosis time for T1DM and greater levels of HbA1c increased the chance of daytime sleepiness.

RESUMO Objetivo: Avaliar as características do sono em crianças e adolescentes portadores de diabetes melito tipo 1 (DM1) e sua relação com o controle glicêmico. Métodos: Estudo transversal realizado em um hospital público de São Paulo. A amostra foi composta de 86 portadores de DM1 entre 10 e 18 anos, aderentes à insulinoterapia, com monitoração mínima de três glicemias capilares ao dia e função tireoidiana normal. Foram avaliados os dados clínicos, antropométricos e laboratoriais de cada paciente. Utilizaram-se a Escala de Sonolência Diurna Pediátrica (ESDP) e o Questionário de Cronotipo de Munique (QCTM). Resultados: A média de hemoglobina glicada (HbA1c) foi 9,2±2,1%, sendo maior em adolescentes. A média do escore da ESDP foi 13,9±4,7. Pacientes com HbA1c<7,5% tiveram menor escore na ESDP e maior duração do sono em dias de semana do que pacientes com HbA1c≥7,5%. Verificaram-se correlações negativas da HbA1c com valores do cronotipo e com duração do sono em dias de semana e correlação positiva da HbA1c com jet lag social. Pacientes com tempo de DM1 menor que três anos tiveram maior prevalência de sonolência diurna. A análise de regressão apontou que, quanto maior a HbA1c e menor o tempo de diagnóstico de DM1, maior a chance de sonolência diurna, independentemente de idade e sexo. Conclusões: Pacientes com HbA1c mais elevada apresentaram mais sonolência diurna, cronotipo matutino, menor duração do sono em dias de semana e maior jet lag social. O menor tempo de diagnóstico de DM1 e HbA1c≥7,5% aumentaram a chance de maior sonolência diurna.

Evaluation of sleep characteristics of children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: To evaluate sleep characteristics of children and adolescents with type 1 diabetes mellitus (T1DM) and their relationship with glycemic control. METHODS: A cross-sectional study was conducted at a public hospital in São Paulo, Brazil. It included 86 patients with T1DM, aged between 10 and 18 years old, who were on insulin therapy, had performed at least three measurements of capillary blood glucose throughout the day, and had normal thyroid function. The clinical, anthropometric, and laboratory data of each patient were evaluated. The Pediatric Daytime Sleepiness Scale (PDSS) and the Munich Chronotype Questionnaire (MCTQ) were used to assess the sleep characteristics. RESULTS: The mean level of glycated hemoglobin (HbA1c) was 9.2±2.1%, and it was higher in adolescents than in children. The mean score of PDSS was 13.9±4.7. Patients with HbA1c<7.5% had lower PDSS scores and longer sleep duration on weekdays than patients with HbA1c≥7.5%. HbA1c levels were negatively correlated with chronotype values and sleep duration on weekdays and positively correlated with social jet lag. Patients who had had T1DM for less than three years had a higher prevalence of daytime sleepiness. The regression analysis showed that higher HbA1c (≥7.5%) and shorter time since the diagnosis of T1DM increased the chance of daytime sleepiness, regardless of age and sex. CONCLUSIONS: Patients with higher HbA1c had more daytime sleepiness, a morning chronotype, shorter sleep duration on weekdays and a more significant social jet lag. The shorter diagnosis time for T1DM and greater levels of HbA1c increased the chance of daytime sleepiness.

A three-step molecular protocol employing DNA obtained from dried blood spots for neonatal screening for 45,X Turner syndrome.

Turner syndrome (TS) is one of the most common human chromosomal abnormalities; it is characterized by the presence of one normal X chromosome and the complete or partial loss of the second X chromosome. The early recognition of TS patients allows for adequate therapy for short stature and pubertal sex steroid substitution. We developed a cost-effective molecular diagnostic tool that can be used to identify 45,X TS patients from dried blood spots, for possible use in neonatal screening for TS. We used a three-step method for 45,X TS detection: i) DNA extraction from dried blood spot samples, ii) pre-PCR HpaII digestion (methylation-sensitive enzyme) and iii) GeneScan analysis of selected cases. DAX-1 gene amplification was used to recognize DNA integrity, and the androgen receptor gene (Xq11-12), which is both a highly polymorphic and methylated gene, was used to determine the number of X chromosome alleles. Using this three-step diagnostic procedure, we detected apparent TS in 1/304 (0.33%) samples; such individuals should be submitted to clinical examination and karyotype confirmation. The three-step 45,X TS neonatal screening protocol is a simple, reliable, fast (under 30 h) and cost-effective diagnostic tool, useful for the neonatal detection of TS.