L225P mutation of ABCC8 gene: a case of transient neonatal diabetes mellitus with thrombophilic predisposition and epilepsy

Neonatal diabetes mellitus (NDM) is defined as a rare disorder of glucose metabolism in the first six months of life, transient (TNDM) or permanent (PNDM). TNDM usually resolves by 18 months, though it might relapse later in life; PNDM requires lifelong therapy with insulin or/and sulfonylurea. Etiology of NDM is monogenic and genetically heterogeneous. TNDM is often caused by an over-expression of paternal genes on chromosome 6 or by mutation in KCNJ11. Either way the release of insulin is reduced. PNDM is mostly associated with two genes, KCNJ11and ABCC8, which encode, respectively, Kir 6.2 and SUR1, subunits of beta cells K-ATP channel. K-ATP channel is constitutively open, hyperglycemia increases the intracellular ATP levels that cause the closure of K-ATP channel and the depolarization of beta cell causing release of insulin. Inactivating mutations in Kir 6.2 or SUR1, K-ATP channel remains open leading to impaired insulin secretion and neonatal diabetes. Here, we report a case of a three months old baby with diagnosis of NDM and thrombophilic predisposition, referred to emergency pediatric department because of intercurrent ipsilateral clonus to the upper and lower right limbs from a few days, successor seizures during the recovery and incidental finding of hyperglycemia. Child was initially treated with insulin, subsequently was started therapy with glybenclamide for 13 months with progressive decal age. The child was also successfully weaned by treatment with sulfonylureas and epilepsy was well controlled with Phenobarbital

A distinctive 'microbial signature' in celiac pediatric patients

<p>Abstract</p> <p>Background</p> <p>Celiac Disease (CD) is an autoimmune disorder of the small intestine in which dietary gluten ingestion leads to a chronic enteropathy. Recently, scientific evidence suggested a potential role of gut microbiota in CD. To have a snapshot of dominant duodenal microbiota we analyzed the mucosa-associated microbiota of 20 children with CD, before and after a gluten-free diet (GFD) regimen, and of 10 controls. Total DNA was extracted from duodenal biopsies and amplification products of 16S ribosomal DNA were compared by temporal temperature gradient gel electrophoresis (TTGE). TTGE profiles were analyzed by statistical multivariate analysis.</p> <p>Results</p> <p>The average number of bands in TTGE profiles was significantly higher (<it>P </it>< 0.0001) in active (n.b. 16.7 ± 0.7) and inactive states (n.b. 13.2 ± 0.8) than in controls (n.b. 3.7 ± 1.3). Mean interindividual similarity index was 54.9% ± 14.9% for active disease, 55.6% ± 15.7% for remission state and 21.8% ± 30.16% for controls. Similarity index between celiac children before and after GFD treatment was 63.9% ± 15.8%. Differences in microbiota biodiversity were among active and remission state (<it>P </it>= 0.000224) and amid active CD and controls (<it>P </it>< 0.001). <it>Bacteroides vulgatus </it>and <it>Escherichia coli </it>were detected more often in CD patients than in controls (<it>P </it>< 0.0001).</p> <p>Conclusions</p> <p>Overall, the results highlighted a peculiar microbial TTGE profile and a significant higher biodiversity in CD pediatric patients' duodenal mucosa. The possible pathophysiological role of these microbial differences needs further characterization.</p

Atrioventricular block associated with Crohn's relapsing colitis in a 12-year-old child.

[No abstract available

5-Aminosalicylates and Renal Function in Children with Inflammatory Bowel Disease

Introduction: drugs containing 5-ASA (aminosalicylates) are widely used in the management of inflammatory bowel disease (IBD) both for treating the active phases and maintaining remission. The use of these agents has been associated with the risk of developing a tubuleinterstitial nephritis although the presence of this injury in IBD patients (pts) who had never received 5-ASA has been reported. There are no studies on the renal function of children with IBD receiving 5-ASA Aim: in a group of children with IBD on 5-ASA therapy we have assessed the renal function and its relationship to the cumulative dose of 5-ASA, disease duration and activity indexes (PCDAI for CD, PUCAI for UC). Methods: We enrolled 23 consecutive children (10 female) (mean age [SD]: 10.0 [5.6] years) with ulcerative colitis (UC), and 13 children (7 female) (mean age [SD]: 12.0 [4.3] years) with Crohn's disease (CD). All were referred to our Department with a diagnosis of IBD for re-evaluation of their condition. All were receiving only 5-ASA. Renal function test was performed by obtaining a 24-hour urine collection and a blood sample drawn at the end of the urine collection. Glomerular filtration rate, fractional excretion of sodium, tubular reabsorption of phosphate and proteinuria were measured. The total drug dose, the total drug dose/kg and the total drug dose/kg/month of therapy were also calculated. Pts were subdivided in two groups on the basis of the proteinuria level, 150mg/die (group B): the latter were compared for renal function, drug dose, and disease duration. Difference between groups was analyzed with non-parametric test (Wilcoxon test) (p 150 mg/ die). A and B groups did not differ for renal function parameters, total drug dose taken, total drug dose/kg and the total drug dose/kg/month of therapy. The disease duration (months) was significantly shorter in children with a proteinuria >150mg/die (CD; A: 48.5±53.6, B: 20.1±9.6 - UC; A: 31.3±33.4, B: 20.2±31.1). The level of proteinuria significantly correlated with the acitivity of disease both for CD (r: 0.77, p<0.01) and for UC (r:0.69, p<0.01). Conclusions: in children with IBD chronic 5-ASA administration does not cause proteinuria; the latter appears to be related to the disease activity. It is suggested that proteinuria can be a feature of extra-intestinal involvement of IBD

The anti-deamidated gliadin peptide antibodies unmask celiac disease in small children with chronic diarrhoea

Objectives: To assess the usefulness of a new class of antibodies, the anti-deamidated gliadin peptides, in the diagnostic approach to children less than 2 years with suspected celiac disease. Patients and methods: We investigated 40 children (median age: 16.8 months; age range: 4-24 months), with symptoms and signs of chronic enteropathy and high serum levels of conventional anti-gliadin antibodies, but normal values of anti-transglutaminase and anti-endomysial antibodies; all underwent measurement of anti-deamidated gliadin peptides serum levels, upper gastrointestinal endoscopy with biopsies and HLA typing; 40 subjects served as controls. Results: In 29 patients (group A) serum levels of anti-deamidated gliadin peptides were normal and duodenal histology showed a spectrum of abnormalities ranging from mucosal inflammatory infiltrates to villous damage (in almost all cases compatible with Marsh 1-to-2 lesions). All improved on a cow's and soy milk free diet containing gluten. In 11 patients (group B) there were high serum levels of anti-deamidated gliadin peptides and histology showed features suggestive of celiac disease (Marsh 2-to-3 lesions) in all; furthermore, human leucocyte antigen typing was consistent with a celiac disease genetic pattern in all. Group B patients significantly improved on a gluten free diet containing cow's and soy milk proteins. None of the control group was anti-deamidated gliadin peptides positive. Conclusions: In children younger than 2 years with signs of chronic enteropathy and normal values of classical serum markers of celiac disease, the latter can be predicted by high serum levels of anti-deamidated gliadin peptides. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

HLA-DQ and risk gradient for celiac disease

Celiac disease (CD) is a rare example of multifactorial disorder in which a genetic test is of great clinical relevance, as the disease rarely develops in the absence of specific HILA alleles. We typed DR-DQ genes in 437 Italian children with celiac disease, 834 first-degree relatives, and 551 controls. Of patients, 91 % carried DQ2 and/or DQ8 heterodimers, 6% only had)32 chain, 2% was alpha 5 positive, and four were DQ2/DQ8/beta 2/alpha 5 negative. Only the presence of alpha 5 resulted negatively associated to disease (p = 2 X 10(-4)), whereas we confirmed the effect of the beta half of DQ2 dimer on CD predisposition (p = 4 x 10(-12)). Considering 1:100 disease prevalence, we obtained a risk gradient ranging from 1:7 for DQ2 and DQ8 individuals down to 1:2518 for subjects lacking all predisposing factors. The DQB1*02 and DQB1*0302 concurrence (p = 9 X 10-4), besides the DQB1*02/*02 homozygosity, had an additional role in disease genetic determination. The CD prevalence rose to 17.6% in sisters, 40.8% in brothers, and 3.4% in parents. In the three groups, the subjects carrying high-risk HLA molecules were 57%, 71%, and 58%; among them, 29%, 15%, and 6% respectively had CD. Those siblings and parents with no susceptible factors were not affected. These findings indicate the impact of the HLA test for CD in clinical practice. (0 2009 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics