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Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

Background: Obesity is the main risk factor for essential hypertension (EH) in childhood. The O.Si.Me. study (Obesity and Metabolic Syndrome in children and adolescents) evaluated the prevalence of metabolic syndrome (MetS) and its constitutive traits in a sample of obese children and adolescents living in Campania, southern Italy. Patients and methods: Four hundred and fifteen children and adolescents consecutively referred to the National Health Service participating Outpatient Clinics for minor health problems and found to have a Body Mass Index (BMI) Z-score > 2.0 were enrolled in the study. The entire sample was screened for MetS, which was defined as the presence of at least 2 of the following alterations in addition to obesity: fasting hyperglycemia, low levels of high-density lipoproteins cholesterol, hypertriglyceridemia, and EH. The present analysis evaluated the clinical characteristics of the O.Si.Me subgroup of EH participants (systolic and/or diastolic BP ≥ 95 th percentile for age, gender and height) as compared with normotensive participants. Results: The prevalence of EH in the O.Si.Me population was 23.6 % (98/415, 48M and 50F.) and two-thirds of the EH participants met the MetS diagnostic criteria. The EH participants featured serum insulin and HOMA-IR levels significantly higher compared with normotensive ones (11.6±0.6 vs. 9.5±0.4 μIU/ml, p = 0.014; 2.6±0.1 vs. 2.2±0.1, p = 0.028 for insulin and HOMA-IR, respectively). These differences were common to boys and girls and remained significant after correction for age, pubertal stage, body weight, length, BMI, gestational age at birth, duration of breastfeeding and anthropometric parental parameters. Accordingly, children and adolescents with EH had a a relative risk of being insulin resistant (defined as a HOMA-IR ≥2.5) significantly greater compared to those without. Moreover, they exhibited higher serum creatinine levels (53.8±7.1 vs. 35.4±6.8 μmol/l, p=0.025) accounting for gender and body weight. Conclusions: More than a quarter of obese children and adolescents meet the diagnostic criteria for EH in the Campania region in southern Italy. These obese boys and girls have an increased prevalence of insulin resistance and apparently an initial reduction in renal function compared with obese children and adolescents with normal BP.

BACKGROUND: Calcium-sensing receptor gene (CaSR) is a candidate to explain susceptibility to calcium kidney stones. Thus, we studied CaSR gene single-nucleotide polymorphisms (SNPs) and haplotypes associated with stones. METHODS: Four hundred and sixty-three calcium stone formers and 213 healthy controls were genotyped for 21 SNPs mapping the whole CaSR gene. CaSR gene structure was studied. SNPs and haplotypes were analysed for association with stones. RESULTS: Three haplotype blocks were identified in the CaSR gene. The first block was characterized by six SNPs and included gene promoters. The rs7652589 and rs1501899 SNPs and the CATTCA haplotype of the first block were significantly more frequent in normocitraturic calcium kidney stone formers than controls. The risk of stones was increased in normocitraturic homozygous patients and heterozygotes for the CATTCA haplotype. The rate of stones was higher in stone formers with the CATTCA haplotype. In a three-generation family, calcium stones were associated with the CATTCA haplotype. The bioinformatic analysis identified a new site for the octamer-binding transcription factor 1 in the presence of the variant alleles at the rs7652589 and rs1501899 SNPs. This transcription factor may downregulate the transcription of vitamin D-dependent genes and the CaSR expression. Conclusion. SNPs and CATTCA haplotype of the CaSR gene first block is associated with kidney stones in normocitraturic patients.