The aim of this study is to evaluate the diagnostic accuracy of vertebral fractures assessment (VFA) in comparison with conventional radiography in identifying vertebral fractures in children and adolescents affected by OI. On 58 patients (33 males, 25 females; age range 1-18 years; 41 children and 17 adolescents) with osteogenesis imperfecta (OI type I, n = 44, OI type III, n = 4; OI type IV, n = 10), lateral spine images by radiographs and by dual-energy X-ray absorptiometry (DXA) were acquired. For vertebral fracture diagnosis, plain radiographs were used as "gold standard" and VFA and morphometric X-ray absorptiometry (MXA) were performed. The visualized vertebrae were 738 (97.9%) by radiographs and 685 (90.9%) by DXA of a total of 754 vertebrae from T4 to L4. VFA and MXA identified, respectively, 129 (74%) and 116 (66%) of the 175 vertebral fractures detected by radiographs. Radiographs identified 36 patients with vertebral fractures, VFA 35 and MXA 41 (6 false positives). On a per vertebra basis, radiographs and VFA had elevated agreement (93.9%; k score 0.81, 95% CI 0.76-0.86), that resulted slightly lower for MXA (90.6%; k score 0.72, 95% CI 0.65-0.78). VFA and MXA demonstrated high sensitivity (95.6 and 94.1 %, respectively) while specificity was 100% for VFA and 90.6% for MXA on a per patient basis; the agreement was excellent for VFA (98.3%; k score 0.96, 95% CI 0.89-1.03) and good for MXA (87.9%; k score 0.73, 95% CI 0.55-0.91). The diagnostic performance parameters resulted better for VFA (sensitivity 95.6%; specificity 100%; PPV 100%; NPV 97.2%), than for MXA (sensitivity 94.1%; specificity 85.4%; PPV 72.7%; NPV 97.2%). The results of our study demonstrate the reliability of VFA for diagnosis of vertebral fractures in children with OI suggesting its use as a more safe and practical alternative to conventional radiography.

Purpose:To evaluate the role of complex alleles, with two or more mutations in cis position, of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in the definition of the genotype-phenotype relationship in cystic fibrosis (CF), and to evaluate the functional significance of the highly controversial L997F CFTR mutation. Methods: We evaluated the diagnosis of CF or CFTR-related disorders in 12 unrelated subjects with highly variable phenotypes. According to a first CFTR mutational analysis, subjects appeared to be compound heterozygotes for a classic mutation and the L997F mutation. A further CFTR mutational analysis was conducted by means of a protocol of extended sequencing, particularly suited to the detection of complex alleles. Results: We detected a new [R117L; L997F] CFTR complex allele in the four subjects with the highest sweat test values and CF. The eight subjects without the complex allele showed the most varied biochemical and clinical outcome and were diagnosed as having mild CF, CFTR-related disorders, or even no disease. Conclusions: The new complex allele partially explains the variable phenotype in CF subjects with the L997F mutation. CFTR complex alleles are likely to have a role in the definition of the genotype-phenotype relationship in CF. Whenever apparently identical CFTR-mutated genotypes are found in subjects with divergent phenotypes, an extensive mutational search is mandatory. Genet Med 2010:12(9):548 -555.

Background: There is growing evidence that non-alcoholic fatty liver disease (NAFLD) is a disease affecting not only the liver but also extrahepatic organs. Aim: To investigate whether in youths NAFLD is associated with extrahepatic complications such as subclinical atherosclerosis, cardiac abnormalities, hypertension, type 2 diabetes, decreased bone mineral density, renal dysfunction, obstructive sleep apnea, and polycystic ovary syndrome. Methods: We systematically reviewed PubMed; Scopus; Embase; and the Cochrane Library databases up to 28 February 2019 and assessed the quality of studies using the Newcastle-Ottawa Scale. Results: Thirty-five articles were selected for this systematic review: fifteen (4627 participants) evaluated the association of NAFLD with subclinical atherosclerosis; four (969 participants) with cardiac abnormalities; two (550 participants) with hypertension; four (1328 participants) with diabetes; six (523 participants) with low bone mineral density; two (865 participants) with renal dysfunction; one with obstructive sleep apnea; and one with polycystic ovary syndrome. Most studies found that youths with NAFLD have increased features of subclinical atherosclerosis; as well as of cardiac alterations. Limited data were available to endorse a solid estimate of the prevalence of diabetes; low mineral density and renal dysfunction in the pediatric NAFLD population. Conclusion: NAFLD-related intermediate CVD outcomes can occur and be detected early in young populations.

Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease (NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome (MetS), like insulin resistance (IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, MetS, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesity-related comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of MetS as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.