Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Autoimmune atrophic gastritis: The role of Helicobacter pylori infection in children.

BACKGROUND: Autoimmune atrophic gastritis (AIG) is very rare in children. Despite a better understanding of histopathologic changes and serological markers in this disease, underlying etiopathogenic mechanisms and the effect of Helicobacter pylori (H pylori) infection are not well known. We aimed to investigate the relation between AIG and H pylori infection in children. MATERIALS AND METHODS: We evaluated the presence of AIG and H pylori infection in fifty-three patients with positive antiparietal cell antibody (APCA). Demographic data, clinical symptoms, laboratory and endoscopic findings, histopathology, and presence of H pylori were recorded. RESULTS: The children were aged between 5 and 18 years, and 28 (52.8%) of them were male. Mean age was 14.7 ± 2.6 years (median: 15.3; min-max: 5.2-18), and 10 (18.8%) of them had AIG confirmed by histopathology. In the AIG group, the duration of vitamin B12 deficiency was longer (P = .022), hemoglobin levels were lower (P = .018), and APCA (P = .039) and gastrin (P = .002) levels were higher than those in the non-AIG group. Endoscopic findings were similar between the two groups. Intestinal metaplasia was higher (P = .018) in the AIG group. None of the patients in the AIG group had H pylori infection (P = .004). One patient in the AIG group had enterochromaffin-like cell hyperplasia. CONCLUSIONS: Our results show that, in children, H pylori infection may not play a role in AIG. AIG could be associated with vitamin B12 deficiency, iron deficiency, and APCA positivity in children. APCA and gastrin levels should be investigated for the early diagnosis of AIG and intestinal metaplasia.

Carotid intima-media thickness and arterial stiffness as early markers of atherosclerosis in pediatric celiac disease.

The association between pediatric celiac disease (CD) and atherosclerosis is unknown. Our aim was to investigate whether pediatric CD patients have an increased risk of atherosclerosis. We evaluated the premature atherosclerosis by pulse wave velocity (PWV) and carotid intima-media thickness (cIMT). A total of 37 CD patients (20 girls, mean age 13±3.3 years) and 36 healthy age and sex matched controls were enrolled. Mean duration of CD was 47.1±32.3 months and 40.5% of patients had positive tissue transglutaminase antibody (tTg) IgA. Total cholesterol level was lower in CD (p=0.026) and cIMT was lower in tTg IgA antibody negative CD (p=0.030). cIMT was significantly correlated with tTg IgA antibody positivity (r=0.336; p=0.042). Adherence to strict gluten-free diet is associated with decreased cIMT, suggesting that gluten withdrawal seems to have a beneficial effect on premature atherosclerosis.

Change of Helicobacter pylori prevalence in a decade among children undergoing endoscopy.

Our aim was to investigate the trend of H. pylori infection among children during the last decade by a retrospective analysis. Reports of children in whom esophago-gastroduodenoscopy was performed at our institution during two periods 2002-2003 and 2012-2013 were seperated into Group I and Group II, respectively. Pathology reports were investigated for gastritis, atrophy and H. pylori presence. A total of 380 children, 131 in Group I and 249 in Goup II were recruited in the study. H. pylori postivity was found to be higher in Group I (% 48.1 and % 23.1, respectively, p < 0.001). Gastritis and atrophy were associated with H. pylori and both were more prevalent in Group I (p < 0.001). Our study demonstrates that H. pylori prevalence is decreasing in a pediatric population undergoing EGD in Ankara. This is the most recent study regarding pediatric H. pylori prevalence change in Turkey that we know of.

Intractable colitis associated with chronic granulomatous disease in a young girl.

Chronic granulomatous disease (CGD) is an autosomal recessive or X-linked disorder caused by NADPH oxidase deficiency leading to an impaired ability of reactive superoxide anion and metabolite formation and recurring severe bacterial and fungal infections, with a high mortality rate. Diarrhea, colitis, ileus, perirectal abscess formation and anal fissures are reported gastrointestinal findings in these patients. We report a case of intractable colitis associated with CGD in a young girl.

Yield of coeliac screening in abdominal pain-associated functional gastrointestinal system disorders.

AIM: Chronic abdominal pain (CAP) in childhood is common and in the majority functional. While CAP is one of the complaints of coeliac disease (CD), whether CAP as a sole complaint is indicative of CD is unclear. Our aim was to evaluate the relationship between CAP and CD. METHODS: The study was conducted on 1047 children (61.1% female, mean age 9.6 ± 4.1 years) with CAP. Patients were evaluated according to the Rome III criteria. Patients with alarm symptoms and conditions known to be associated with CD were excluded. Patients were screened for CD using a rapid tissue transglutaminase (tTG) test; positive cases were tested by tTG ELISA, and duodenal biopsies were obtained if tTG was above the normal limit. RESULTS: Functional dyspepsia (FD), irritable bowel syndrome (IBS) and functional abdominal pain (FAP) were diagnosed in 384 (36.7%), 274 (26.2%) and 389 (37.2%) patients, respectively. In 13 patients, the tTG rapid test was positive; 10 were also positive for tTG by ELISA and histopathological evaluations diagnosed CD in all 10 patients. The overall prevalence of CD was 0.95% (2.2%, 0.5% and 0.5% in patients with IBS, FD and FAP, respectively). The prevalence of CD in patients with IBS was higher than expected but with borderline statistical significance (P = 0.053). CONCLUSIONS: CD is found as common in children with FD and FAP as in the general population. CD was more commonly diagnosed in IBS patients with borderline statistical significance. We suggest that particular attention be paid to children with IBS.

Atypical manifestation of LRBA deficiency with predominant IBD-like phenotype.

BACKGROUND: Inflammatory bowel diseases (IBDs) denote a heterogeneous group of disorders associated with an imbalance of gut microbiome and the immune system. Importance of the immune system in the gut is endorsed by the presence of IBD-like symptoms in several primary immunodeficiencies. A fraction of early-onset IBDs presenting with more severe disease course and incomplete response to conventional treatment is assumed to be inherited in a Mendelian fashion, as exemplified by the recent discovery of interleukin (IL)-10 (receptor) deficiency. METHODS: We analyzed a patient born to consanguineous parents suffering from severe intestinal manifestations since 6 months of age and later diagnosed as IBD. Eventually, she developed autoimmune manifestations including thyroiditis and type I diabetes at the age of 6 and 9 years, respectively. Combined single-nucleotide polymorphism array-based homozygosity mapping and exome sequencing was performed to identify the underlying genetic defect. Protein structural predictions were calculated using I-TASSER. Immunoblot was performed to assess protein expression. Flow cytometric analysis was applied to investigate B-cell subpopulations. RESULTS: We identified a homozygous missense mutation (p.Ile2824Pro) in lipopolysaccharide-responsive and beige-like anchor (LRBA) affecting the C-terminal WD40 domain of the protein. In contrast to previously published LRBA-deficient patients, the mutant protein was expressed at similar levels to healthy controls. Immunophenotyping of the index patient revealed normal B-cell subpopulations except increased CD21 B cells. CONCLUSIONS: We describe a patient with a novel missense mutation in LRBA who presented with IBD-like symptoms at early age, illustrating that LRBA deficiency should be considered in the differential diagnosis for IBD(-like) disease even in the absence of overt immunodeficiency.