Renal manifestations of tuberous sclerosis complex: patients' and parents' knowledge and routines for renal follow-up - a questionnaire study.

BACKGROUND: Renal angiomyolipomas (AMLs) are a major clinical feature in patients with tuberous sclerosis complex (TSC). Spontaneous bleeding can be life threatening, and appropriate information and proper surveillance and management are important to limit morbidity and mortality. Because TSC is a rare disease, patients are at risk of suboptimal medical management. Our aim was to investigate patients' and parents' knowledge about renal angiomyolipomas (AMLs) in Tuberous Sclerosis Complex (TSC) and to identify current routines for renal follow-up. METHODS: A questionnaire survey was initiated by the French Reference Centre on TSC. It was distributed in France through university hospitals and the patients' association (2009-2011), and to patients registered by the Norwegian National Centre for Rare Epilepsy-Related Disorders (2013-2014). Contingency tables with Chi-Square test for independence (with Yates Continuity Correction) and Pearson-Chi-Square value were used for correlation statistics. RESULTS: We included 357 patients (France, n=257; Norway n=100). Most participants knew that TSC is associated with AMLs. However, 42 % did not know about the risk of AMLrelated bleeding, and 37 % had been informed about the risk of bleeding only after the age of 15 years. Furthermore, 14 % did not know whether they themselves or their child had AMLs. Patients had less knowledge than parents. Medical consultations and patient associations were the main sources of information. Among 30 % of patients, renal imaging was not received at all, or not conducted every 1-3 years, as recommended by current guidelines. Regular imaging was more frequent in patients with AMLs < 15 years, than in patients with AMLs ≥ 15 years. Ultrasound was the most frequently used imaging modality. CONCLUSIONS: Knowledge of renal AML in TSC patients and their parents was lower than expected, and follow-up by renal imaging was suboptimal for a substantial proportion of patients. Patients and parents should be informed about the risk and symptoms of renal bleeding, at the latest when the patient is 15 years. Monitoring the growth of AMLs should be standardized to comply with guidelines. Transition between adolescence and adulthood is a high-risk period and ensuring appropriate follow-up at this time is particularly important.

A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma.

Type 1 diabetes (T1D) and allergic asthma are immune-mediated diseases. Pattern recognition receptors are proteins expressed by cells in the immune system to identify microbial pathogens and endogenous ligands. Toll-like receptors (TLRs) and CD14 are members of this family and could represent a molecular link between microbial infections and immune-mediated diseases. Diverging hypotheses regarding whether there exists a common or inverse genetic etiology behind these immune-mediated diseases have been presented. We aimed to test whether there exist common or inverse associations between polymorphisms in the pattern recognition receptors TLR2, TLR4 and CD14 and T1D and allergic asthma. Eighteen single nucleotide polymorphisms (SNPs) were genotyped in TLR2 (2), TLR4 (12) and CD14 (4) in 700 T1D children, 357 nuclear families with T1D children and 796 children from the 'Environment and Childhood Asthma' study. Allele and haplotype frequencies were analyzed in relation to diseases and in addition transmission disequilibrium test analyses were performed in the family material. Both T1D and allergic asthma were significantly associated with the TLR2 rs3804100 T allele and further associated with the haplotype including this SNP, possibly representing a susceptibility locus common for the two diseases. Neither TLR4 nor CD14 were associated with T1D or allergic asthma.

Joint effects of HLA, INS, PTPN22 and CTLA4 genes on the risk of type 1 diabetes.

BACKGROUND/HYPOTHESIS: HLA, INS, PTPN22 and CTLA4 are considered to be confirmed type 1 diabetes susceptibility genes. HLA, PTPN22 and CTLA4 are known to be involved in immune regulation. Few studies have systematically investigated the joint effect of multiple genetic variants. We evaluated joint effects of the four established genes on the risk of childhood-onset type 1 diabetes. METHODS: We genotyped 421 nuclear families, 1,331 patients and 1,625 controls for polymorphisms of HLA-DRB1, -DQA1 and -DQB1, the insulin gene (INS, -23 HphI), CTLA4 (JO27_1) and PTPN22 (Arg620Trp). RESULTS: The joint effect of HLA and PTPN22 on type 1 diabetes risk was significantly less than multiplicative in the case-control data, but a multiplicative model could not be rejected in the trio data. All other two-way gene-gene interactions fitted multiplicative models. The high-risk HLA genotype conferred a very high risk of type 1 diabetes (OR 20.6, using the neutral-risk HLA genotype as reference). When including also intermediate-risk HLA genotypes together with risk genotypes at the three non-HLA loci, the joint odds ratio was 61 (using non-risk genotypes at all loci as reference). CONCLUSION: Most established susceptibility genes seem to act approximately multiplicatively with other loci on the risk of disease except for the joint effect of HLA and PTPN22. The joint effect of multiple susceptibility loci conferred a very high risk of type 1 diabetes, but applies to a very small proportion of the general population. Using multiple susceptibility genotypes compared with HLA genotype alone seemed to influence the prediction of disease only marginally.

[Tuberculosis in Norwegian children--diagnostic challenges]. / Tuberkulose hos barn i Norge--diagnostiske utfordringer.

BACKGROUND: Each year, 20-25 Norwegian children below the age of 18 are diagnosed with tuberculosis in Norway. MATERIAL AND METHODS: As a demonstration of various difficulties in the work-up and diagnosis of tuberculosis, we present eight infected children aged 15 months to 10 years. RESULTS: Children often contract the infection from adults and may develop serious manifestations including miliary tuberculosis and meningitis. The symptoms are often not specific and tuberculosis may be mistaken for other diseases. Delay and inappropriate diagnostics may have deleterious consequences. INTERPRETATION: The main message is to start treatment upon clinical suspicion of tuberculosis. It is mandatory to sample the necessary biological material for microbiological tests before starting treatment.