CYP21A2 Gene Pathogenic Variants: A Multicenter Study on Genotype-Phenotype Correlation from a Portuguese Pediatric Cohort.

BACKGROUND: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder characterized by 3 overlapping phenotypes: salt-wasting (SW), simple virilizing (SV), and non-classic (NC). We aimed at conducting a nationwide genotype description of the CAH pediatric patients and to establish their genotype-phenotype correlation. METHODS: CAH patients were recruited from Portuguese pediatric endocrinology centers and classified as SW, SV, or NC. Genetic analysis was performed by polymerase chain reaction (sequence specific primer, restriction fragment length polymorphism) or direct Sanger sequencing. Genotypes were categorized into 4 groups (0, A, B, and C), according to their predicted enzymatic activity. In each group, the expected phenotype was compared to the observed phenotype to assess the genotype-phenotype correlation. RESULTS: Our cohort comprises 212 unrelated pediatric CAH patients (29% SW, 11% SV, 60% NC). The most common pathogenic variant was p.(Val282Leu; 41.3% of the 424 alleles analyzed). The p.(Val282Leu) variant, together with c.293-13A/C>G, p.(Ile173Asn), p.(Leu308Thr), p.(Gln319*), and large deletions/conversions were responsible for 86.4% of the mutated alleles. Patients' stratification by disease subtype revealed that the most frequent pathogenic variants were c.293-13A/C>G in SW (31.1%), p.(Ile173Asn) in SV (46.9%), and p.(Val282Leu) in NC (69.5%). The most common genotype was homozygosity for p.(Val282Leu; 33.0%). Moreover, we found 2 novel variants: p.(Ile161Thr) and p.(Trp202Arg), in exons 4 and 5, respectively. The global genotype-phenotype correlation was 92.4%. Group B (associated with the SV form) showed the lowest genotype-phenotype correlation (80%). CONCLUSION: Our cohort has one of the largest NC CAH pediatric populations described. We emphasize the high frequency of the p.(Val282Leu) variant and the very high genotype-phenotype correlation observed.

Overweight in youth and sleep quality: is there a link?

ABSTRACT Objective Overweight seems to be related to a higher prevalence of sleep disturbances. Decreased sleep duration and altered sleep quality are risk factors for obesity. Our aim was to compare the sleep pattern of overweight children with that of a matched control group and assess the relationship between sleep quality and obesity. Materials and methods Retrospective cohort study comparing 41 overweight children with a normal-weight control group, both submitted to polysomnography. The samples were matched for age, sex, and apnea-hypopnea index. Body mass index (BMI) z-scores were calculated using World Health Organization (WHO) growth charts. Insulin resistance in the study group was determined using the homeostatic model assessment for insulin resistance (HOMA-IR). Sleep patterns were compared. The statistical analysis was performed using SPSS® version 21. Results The mean age (± standard deviation) of the population was 10 ± 3.4 years (min. 5 years; max. 17 years). Fifty-six percent of the participants in both groups were girls. N3% was lower in the study group (18.95 ± 6.18%) compared with the control group (21.61 ± 7.39%; t (40) = 2.156, p = 0.037). We found a correlation in the study group between HOMA-IR and N3% (Rs = -0.434, p = 0.008). Conclusion The present study suggests a link between overweight/obesity and altered sleep quality due to compromised non-rapid eye movement sleep, an indirect marker of sleep quality. There was also a link between slow-wave sleep duration and insulin resistance. We must find a strategy to provide adequate slow-wave sleep duration to reduce the obesity epidemic at young ages. Further research is needed.

Overweight in youth and sleep quality: is there a link?

OBJECTIVE: Overweight seems to be related to a higher prevalence of sleep disturbances. Decreased sleep duration and altered sleep quality are risk factors for obesity. Our aim was to compare the sleep pattern of overweight children with that of a matched control group and assess the relationship between sleep quality and obesity. MATERIALS AND METHODS: Retrospective cohort study comparing 41 overweight children with a normal-weight control group, both submitted to polysomnography. The samples were matched for age, sex, and apnea-hypopnea index. Body mass index (BMI) z-scores were calculated using World Health Organization (WHO) growth charts. Insulin resistance in the study group was determined using the homeostatic model assessment for insulin resistance (HOMA-IR). Sleep patterns were compared. The statistical analysis was performed using SPSS® version 21. RESULTS: The mean age (± standard deviation) of the population was 10 ± 3.4 years (min. 5 years; max. 17 years). Fifty-six percent of the participants in both groups were girls. N3% was lower in the study group (18.95 ± 6.18%) compared with the control group (21.61 ± 7.39%; t (40) = 2.156, p = 0.037). We found a correlation in the study group between HOMA-IR and N3% (Rs = -0.434, p = 0.008). CONCLUSION: The present study suggests a link between overweight/obesity and altered sleep quality due to compromised non-rapid eye movement sleep, an indirect marker of sleep quality. There was also a link between slow-wave sleep duration and insulin resistance. We must find a strategy to provide adequate slow-wave sleep duration to reduce the obesity epidemic at young ages. Further research is needed.

[Cardiovascular risk factors and childhood obesity]. / Factores de risco cardiovascular e obesidade infantil.

BACKGROUND: Even in pediatric age, obesity is associated to cardiovascular risk factors such as dyslipidemia, high blood pressure and metabolic syndrome, which contribute to increased morbidity and mortality in adulthood. AIMS: characterize the prevalence of cardiovascular risk factors in obese children and adolescents followed in pediatric endocrinology. METHODS: retrospective analysis of cases followed between January 1997 and June 2008, with age between two and eighteen years. Data analyzed included demographic, epidemiological and clinical parameters. BMI z-score, blood pressure, lipid profile and insulinresistance were also studied. RESULTS: We evaluated 886 children with a mean age of 9.4 years (SD ± 3.5), 53.6% female and 60% with android type obesity. The lipid profile was altered in 42.1% of children. Children with dyslipidemia were younger than children without dyslipidemia (9.4 ± 3.33 vs 9.56 ± 3.33, p-0.62) and were predominantly male (55.2% vs 41.1%, p<0.001). There was not a statistically significant difference in z-score between the two groups. High blood pressure was found in 32% of cases. In these cases, the mean z-score was significantly higher (2.4 ± 0.54 vs 2.27 ± 0.49; p-0.001). There was not a statistically significant difference in distribution according to age and gender. Metabolic syndrome criteria's were found in 5.6% of cases and two children with type two Diabetes Mellitus were registered. CONCLUSION: in the studied population we found a worrying number of obese children with risk factors for cardiovascular disease. In addition to short term complications, the risk of coronary disease and atherosclerosis in adulthood is high, so it is essential an early screening and surveillance program.

[Overweight and obesity - prevention in the school]. / Excesso de peso e obesidade - prevenção na escola.

INTRODUCTION: The prevalence of the childhood obesity through the last decades is increasing, with significant comorbidities and major health consequences. Children's food habits are influenced by family, friends, school and the media. Successful interventions for preventing childhood obesity must include nutrition education, physical activity, school-based programs, family participation and counseling. AIMS: To evaluate the prevalence of overweight and obesity among children and adolescents in an urban area in Lisbon and to implement a school-based program to prevent obesity. METHODOLOGY: A cross sectional study was performed in children and adolescents attending the public school in an urban area of Lisbon. Learning sessions regarding obesity were performed. FINDINGS: The study included 1875 children and adolescents, with ages between five and 17 years. The overall prevalence rate found for overweight and obesity was 21% and 9,5%, respectively. CONCLUSION: Obesity and overweight are important problems in children and adolescents. School-based programs can have an important role in preventing this disease.

[Microlithiasis and testicular tumour]. / Microlitíase e tumor testicular.

Testicular microlithiasis is a rare entity, usually asymptomatic and bilateral. There are however reports that until 40% of the cases may be related with testicular tumours. We report an 11-year-old boy, with a four-month history of left testicular mass. Sonography showed increased volume of left testis and bilateral microlithiasis. Testicular biopsy revealed Sertoli cell tumour and he was submitted to left radical orquidectomy. Testicular cancer is often curable, especially if diagnosed and treated early. The association of malignancy justifies long term clinical and ultrasound follow-up of testicular microlithiasis.