Universal screening for familial hypercholesterolemia in 2 populations.

PURPOSE: In Europe, >2 million individuals with familial hypercholesterolemia (FH) are currently undiagnosed. Effective screening strategies for FH diagnosis in childhood are urgently needed. We assessed the overall performances of 2 different FH screening programs in children: universal screening program with opt-out and opt-in type participation. METHODS: We analyzed the data from 2 independent populations based on >166,000 individuals screened for hypercholesterolemia. Genetic analyses of FH-related genes were finalized in 945 children and 99 parents. RESULTS: A total of 305 (32.3%) children were genotyped as positive or with a variant of uncertain significance in FH-related genes. For low-density lipoprotein cholesterol levels of 3.5 mmol L (135.3 mg/dL), the overall sensitivity and specificity for confirming FH were 90.5% and 55.3%, respectively. As part of child-parent screening, in >90% of the families, the parent with reported higher cholesterol levels was positive for the familial genetic variant. The cohort-based prevalence of FH from the opt-out universal screening program was estimated to be 1 in 431 individuals (95% CI = 1/391-1/472). CONCLUSION: Universal 3-step FH screening approach in children enabled detection of most children and their parents in every generation screened at reasonable costs. Opt-out screening strategy might be preferable over opt-in screening strategy.

An Adolescent Boy with Klinefelter Syndrome and 47,XXY/46,XX Mosaicism: Case Report and Review of Literature.

Klinefelter syndrome is the most commonly reported sex chromosome abnormality. It is heavily underdiagnosed due to the substantial variability of clinical presentations but is generally characterized by small, firm testes, hypergonadotropic hypogonadism, and the absence of spermatogenesis. Most patients with Klinefelter syndrome have a 47,XXY genotype. If they present with mosaicism, two different cell lines are usually identified, an aneuploid 47,XXY cell line and a normal male 46,XY cell line. There are very few cases of 47,XXY mosaicism with the additional female cell line 46,XX described in the literature. We report a case of an adolescent with the male phenotype and a rare variant mosaic 47,XXY/46,XX karyotype who presented with painless bilateral gynaecomastia. 47,XXY and 46,XX mosaic cell lines were identified with GTG-banding and further characterized using fluorescent in situ hybridization. We summarized the available clinical presentations of reported male patients with 47,XXY/46,XX mosaicism. To improve the clinical management and quality of life in individuals with rare and cryptic genomic imbalances, the genetic diagnosis would need to be extended to atypical cases.

Evaluation of Body Mass Index, Overweight and Obesity Status, and Cholesterol Levels in Younger Children.

This cohort study examines cholesterol levels in children with overweight or obesity.

Stabilization of Overweight and Obesity in Slovenian Adolescents and Increased Risk in Those Entering Non-Grammar Secondary Schools.

BACKGROUND/AIM: To estimate overweight and obesity prevalence trends in Slovenian adolescents entering secondary schools in the years 2004, 2009 and 2014 and differences in the prevalence between different types of secondary schools. METHODS: Data from 17,538 adolescents entering secondary schools (mean age ± standard deviation 15.4 ± 0.5 years) collected during obligatory medical examination in years 2004, 2009 and 2014 was analyzed. Overweight and obesity were defined using International Obesity Task Force criteria. RESULTS: In 2004-2009 overweight and obesity prevalence increased, especially in males and stabilized thereafter (2009-2014) in both genders. It was significantly higher (p < 0.0001) in those attending secondary vocational and technical/professional versus grammar schools (2009; 28.7 vs. 16.8% overweight females and 31.6 vs. 22.3% overweight males; 2014: 29.7 vs. 17.9% overweight females and 33.6 vs. 20.4% overweight males). CONCLUSIONS: Overweight and obesity prevalence in Slovenian adolescents entering secondary schools stabilized recently. Adolescents attending secondary vocational and technical/professional schools are at an increased risk of overweight and obesity.

Autoimmune hepatitis as a presenting manifestation of mixed connective tissue disease in a child. Case report and review of the literature.

BACKGROUND: Liver disease is rare in the course of mixed connective tissue disease. Most commonly liver steatosis or elevated liver function tests are reported and only a few cases of mixed connective tissue disease associated with autoimmune hepatitis were described. CASE PRESENTATION: We report a case of an 11-year old boy with hepatitis on admission to the hospital and symptoms and signs of mixed connective tissue disease. Autoimmune hepatitis has been confirmed by liver biopsy. CONCLUSION: To the best of our knowledge this is the youngest patient with autoimmune hepatitis as a presenting manifestation of mixed connective tissue disease.

Decreased prevalence of hypercholesterolaemia and stabilisation of obesity trends in 5-year-old children: possible effects of changed public health policies.

BACKGROUND: Overweight/obesity in children is a worldwide public health problem. Together with hypercholesterolaemia they are associated with early atherosclerotic complications. OBJECTIVES: In this study, we aimed to investigate the anthropometric characteristics and total cholesterol (TC) levels in a population of 5-year-old children, to determine trends in the prevalence of overweight/obesity and hypercholesterolaemia in 5-year-old children over a period of 8 years (2001-2009) and to assess the impact of modified national nutritional guidelines for kindergartens implemented in 2005. DESIGN: Cross-sectional studies of overweight/obesity prevalence in the years 2001, 2003-2005 and 2009, and hypercholesterolaemia in years 2001 and 2009, in 5-year-old children. SUBJECTS: Altogether, 12 832 (6308 girls/6524 boys) children were included. METHODS: Overweight/obesity was defined by IOTF criteria. Hypercholesterolaemia was defined by TC level >5 mmol/l. Multivariable logistic regression models were used. RESULTS: NO CORRELATION BETWEEN BMI VALUES AND TC LEVELS WAS FOUND. OVERWEIGHT AND OBESITY PREVALENCE WERE STABILISED FROM 2001 TO 2009 (ODDS RATIO (OR) (95% CI): 1.13 (0.99-1.3) and 1.13 (0.89-1.42) respectively). Girls were more frequently overweight/obese than boys (OR (95% CI): 0.71 (0.65-0.79) and 0.75 (0.64-0.89) respectively). Prevalence of hypercholesterolaemia significantly decreased from 2001 to 2009 (OR (95% CI): 0.47 (0.41-0.55)). It was less frequent in boys than in girls (OR (95% CI): O.7 (0.61-0.8)). CONCLUSIONS: This is the first study to describe a negative trend in the prevalence of hypercholesterolaemia in pre-pubertal children. In addition, the prevalence of overweight/obesity in these children has been stabilised. Nationwide changes in public health policies could have influenced these observations.