Genomic testing identifies monogenic causes in patients with very early-onset inflammatory bowel disease: a multicenter survey in an Iranian cohort.

Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. This multicenter study was carried out on 16 Iranian patients with VEO-IBD. We reviewed clinical and basic immunologic evaluation including flow cytometry and immunoglobulin levels. All patients underwent clinical whole exome sequencing (WES). Sixteen patients (8 females and 8 males) with a median age of 43.5 months were enrolled. The median age at the onset of symptoms was 4 months. Most patients (12, 75%) had consanguineous parents. Chronic non-bloody diarrhea (13, 81.3%) and perianal diseases including perianal abscess (6, 37.5%), anal fissure (6, 37.5%), or anal fistula (2, 12.5%) were the most common manifestations. WES identified a spectrum of genetic variants in 13 patients (81.3%): IL10RB (6, 37.5%), MVK (3, 18.8%), and CASP8, SLC35C1, G6PC3, and IKBKB in 1 patient, respectively. In 3 patients (18.7%), no variant was identified. Flow cytometry identified a spectrum of abnormalities that helped to assess the evidence of genetic diagnosis. At the end of the survey, 3 (18.8%) patients were deceased. This high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD.

A dual H-type tracheoesophageal fistula; why not being repaired simultaneously? A case report and review of literature.

BACKGROUND: H-type Tracheoesophageal Fistula (TEF) is a particular type of congenital esophageal anomalies, in which patients present with non-specific symptoms that can result in delayed diagnosis. Here, we report two pediatric cases with a rarer variant called ?dual H-type TEFË®. CASE PRESENTATION: We present two cases of H-type TEF. The first was a 45-day-old boy with feeding problem and cyanosis while feeding, and the second was a three-month-old girl with cough and choking after feeding from the first day of birth. In both cases, two separate TEFs were detected during diagnostic evaluation by flexible bronchoscopy. Both were repaired simultaneously through a cervical incision. The first patient deteriorated 13 days after the surgery, disturbancing in acid-base balance and expired unfortunately. CONCLUSION: Hence, it is necessary to consider the possibility of double TEF in any newly diagnosed H-type TEF.

The association of fecal calprotectin and respiratory exacerbation in cystic fibrosis patients.

BACKGROUND: CF patients experience several episodes of pulmonary exacerbations and reduction in their lung function progressively. Lung function is not the only diagnostic index by physicians to decide if CF patients require antibiotic therapy following pulmonary exacerbations. Non-invasive fecal indicators are increasingly being used to assess intestinal inflammation. Calprotectin is the most extensively utilized fecal biomarker in recent CF researches. METHODS: In this longitudinal study, 30 CF patients (1-18 years) without current infectious gastroenteritis were recruited from Mofid Children's Hospital and Masih Daneshvari Hospital, Tehran, Iran. Then, fecal calprotectin levels were evaluated before treatment, two weeks after systemic antibiotic administration, as well as recurrence of pulmonary exacerbation after first post-hospital discharge. RESULTS: The initial fecal calprotectin level in CF patients receiving antibiotics was 651.13 ± 671.04, significantly decreasing two weeks after antibiotic therapy and following recurrence (171.81 ± 224.40, 607.93 ± 549.89, respectively; P < 0.01). Following systemic antibiotic treatment, the patient's respiratory and GI symptoms improved (P < 0.01). CONCLUSION: Our findings revealed that fecal calprotectin modifications are associated with CF pulmonary exacerbations and antibiotic treatment could reduce calprotectin levels. Therefore, the fecal calprotectin level could be considered as a diagnostic tool and an index to follow the response to treatment in CF pulmonary exacerbations.

Blood lead concentrations among pediatric patients with abdominal pain: a prospective cross-sectional study.

BACKGROUND: Lead exposure is one of the most menacing of environmental exposures, particularly in children. Children are more susceptible to the effects of lead which manifest in many organ systems, including interference with mental and motor development. Lead poisoning can cause colicky abdominal pain. In this study, the authors sought to evaluate the prevalence of elevated blood lead level (BLL) and its contributing factors among pediatric patients presenting with abdominal pain. An epidemic of lead poisoning in adults was previously uncovered, and thus a concern for pediatric lead poisoning was raised. METHODS: Pediatric patients presenting to two pediatric clinics in Tehran with abdominal pain were eligible for enrollment in a descriptive prospective cross-sectional study. A predesigned questionnaire was filled for each patient by their consenting parents. The questionnaire queried demographic information, environmental, social, and other relevant parameters for lead exposure. After completion of the questionnaire, biometrics were obtained, and a blood sample was taken from each patient for measurement of BLL and complete blood count. RESULTS: A total of 187 patients were enrolled in the study. Of them, almost 20% had BLL ≥ 5 µg/dL. Univariate analysis showed that age (p = 0.002, OR 3.194, CI 95% 1.504-6.783), weight (p = 0.009, OR 2.817, CI 95% 1.266-6.269), height (p = 0.003, OR 3.155, CI 95% 1.443-6.899), and playing with both plastic and cotton toys (p = 0.03, OR 2.796, CI 95% 1.072-7.295) were significant predictors of high BLLs. Maternal level of education correlated with blood lead concentrations (p = 0.048, OR 2.524, CI 95% 1.006-6.331). CONCLUSIONS: A clinically significant number of cases of abdominal pain may have high BLLs. Specific attention should be paid to children presenting with abdominal pain, especially due to the detrimental effects of lead on their mental and motor development.

Microbial contamination of home nebulizers in children with cystic fibrosis and clinical implication on the number of pulmonary exacerbations.

BACKGROUND: Early detection of pulmonary contamination in children with cystic fibrosis (CF) is essential since these children are vulnerable to Pseudomonas aeruginosa (P. aeruginosa) colonization. In Iran, home nebulization of antibiotics is a widespread practice in treatment for patients with CF and, to the best our knowledge, no bacteriological surveys have been conducted till date in this regard. METHOD: This observational, cross sectional study was conducted on 61 children with CF at Mofid Children's Hospital, Tehran, from September 2017 to march 2018. The swab sampling was performed from 61 home nebulizers used by children diagnosed with CF. Contemporaneous sputum sample or deep nasopharyngeal swab was taken from each patient for bacterial and fungal testing. Medical records of the patients were reviewed and the number of exacerbations were recorded over the last 12 months prior to the study enrollment. RESULTS: The results of study showed that, 43 (70.5%) nebulizers were contaminated; 31 (50.8%) mouthpieces, 21 (34.4%) reservoirs, and 11 (18%) connecting tubes. The most common organism to be isolated was P. aeruginosa and was recovered from 19 (31%) nebulizers, 16 of them belonged to patients chronically colonized with P. aeruginosa. The remaining three had at least one positive sputum culture for P. aeruginosa in the past 1 year before the study. There was a significant increase in the number of CF exacerbations with an average number of exacerbation being 1.5 ± 1(SD) over last 12 months in children who had pathogenic organisms recovered from their home nebulizers compared with 0.4 ± 0.7(SD) exacerbations per year in whom non-pathogenic organisms were isolated from their nebulizers (P < 0.001). CONCLUSION: The majority of domiciliary nebulizers used by children with CF were contaminated with microorganisms indicating that the nebulizers may serve as potential reservoirs of pathogens for the patients' lung. Perpetuating colonization is a possible concern in the ones recently colonized with P. aeruginosa and, therefore, decontamination of nebulizer requires more attention to prevent ongoing infection. The negative impact of contamination of nebulizer on CF exacerbation requires serious attention and further investigations.

Pediatric liver transplantation and COVID-19: a case report.

BACKGROUND: Immunosuppressed patients, including individuals with organ transplantation, have been among susceptible groups with regard to COVID-19, on the other hand pediatric patients more commonly undergo a mild clinical course after acquiring COVID-19. To the best of the authors knowledge, to this date very little data exists on COVID-19 in a pediatric patient with liver transplantation. CASE PRESENTATION: We report a three year-old boy who had liver transplantation at 18 months old. He was admitted due to dyspnea with impression of acute respiratory distress syndrome and was then transferred to the intensive care unit. Chest X-ray at admission showed bilateral infiltration. Vancomycin, meropenem, azithromycin, voriconazole and co-trimoxazole were started from the first day of admission. On day 4 of admission, with suspicion of COVID-19, hydroxychloroquine, lopinavir/ritonavir and oseltamivir were added to the antibiotic regimen. PCR was positive for COVID-19. The patient developed multi-organ failure and died on day 6 of admission. CONCLUSIONS: For pediatric patients with organ transplantations, extreme caution should be taken, to limit and prevent their contact with COVID-19 during the outbreak, as these patients are highly susceptible to severe forms of the disease.

Evaluating the association between neonatal mortality and maternal high blood pressure, heart disease and gestational diabetes: A case control study.

BACKGROUND: Prevention of noncommunicable diseases (NCDs) during pregnancy is recommended due to severe complications for mothers and infants. Considering that NCDs have a significant impact on infant mortality, this study was conducted to investigate the relationship between mothers' underlying diseases and gestational diabetes and infant mortality in Iran. MATERIALS AND METHODS: Mothers who referred to the health centers in nine provinces of Iran were included. This case-control study used data collected from pregnant women. There were 1162 cases and 1624 controls. The required data were collected from mothers' health records and through interviews. RESULTS: The chances of neonatal mortality in women with a body mass index (BMI) of 30-35, 1.7 times (odds ratio [OR] = 1.7, confidence interval [CI]: 1.19-2.44, P = 0.003) was higher compared with women with a normal BMI. The chance of neonatal mortality among mothers with high blood pressure was three times higher compared with healthy mothers (OR = 3.04, 95% CI: 1.98-4.65, P < 0.001). The chance of neonatal mortality in women with kidney disease was also 1.64 times higher than mothers without kidney problems (OR = 1.64, 95% CI: 1.1-2.45, P = 0.015). In the study of gestational diabetes, the chance of neonatal mortality among the mothers who had at risk was 1.63 times higher than mothers without gestational diabetes (OR = 1.63, 95% CI: 0.84-3.16, P = 0.014). Furthermore, the chance of neonatal mortality among the mothers who had heart disease was 1.10 times higher than mothers without heart disease (OR = 2.10, 95% CI: 0.88-4.99, P = 0.014). CONCLUSION: This study showed that undiagnosed underlying diseases were related to neonatal mortality, which highlights the importance of caring for and counseling about the underlying diseases, screening, and controlling blood sugar levels before and during pregnancy to prevent infant mortality by all means possible.

Food allergy among Iranian children with inflammatory bowel disease: A preliminary report.

BACKGROUND: Evidence has shown a link between allergic disease and inflammatory bowel diseases (IBDs). We investigated food allergy in Iranian pediatric IBD patients. MATERIALS AND METHODS: A cross-sectional study was conducted on a consecutive sample of children with newly diagnosed IBD referring to Mofid Children's University Hospital in Tehran (Iran) between November 2013 and March 2015. Data on age, gender, history of cow's milk allergy (CMA), IBD type, routine laboratory tests, and colonoscopic and histopathological findings were gathered. Food allergy was assessed with the skin prick test (SPT). RESULTS: A total of 28 patients including 19 ulcerative colitis (UC), 7 Cronh's disease (CD), and two with unclassified colitis with a mean age of 8.3 ± 4.4 years. (57.1% females, 42.9% were studied. History of CMA was present in eight patients (28.6%). Seventeen patients (60.7%) had at least one food allergy (68.4% of UC vs. 42.9% of CD, P = 0.230). Ten patients (35.7%) had multiple food allergies (36.8% of UC vs. 42.9% of CD, P > 0.999). Common allergic foods were cow's milk (28.6%), beef, seafood, albumen, wheat, and walnuts (each 10.7%), and peanuts and chestnuts (each 7.1%). The SPT showed CMA in 68.4% (8/17) of UC but none of the CD patients (P = 0.077). CONCLUSION: Food allergy is frequent in Iranian pediatric IBD patients with CMA being the most common observed allergy. The CMA seems to be more frequent in UC than in CD patients.

A rare immunological disease, caspase 8 deficiency: case report and literature review.

BACKGROUND: Caspase-8 is a molecule in the FAS pathway that initiates apoptosis. One of the rarest autoimmune lymphoproliferative syndromes is caspase-8 deficiency. Immunodeficiency, splenomegaly, and lymphadenopathy are the common symptoms of this condition. CASE PRESENTATION: A two-year-old boy entered this study with a fever of unknown origin (FUO) and dysentery. Moreover, he suffered from failure to thrive and was allergic to the cow's milk protein. His fever and dysentery did not respond to antibiotic therapy. The colonoscopy revealed diffuse ulcerations regions in the sigmoid along with skipped areas, mimicking Crohn's disease aphthous lesions. He represented very early-onset inflammatory bowel disease (IBD) and was diagnosed with the caspase-8 deficiency. CONCLUSION: There can be diarrhea or dysentery as the first or main symptoms of inborn errors of immunity (IEIs). The cause of diarrhea and dysentery in this case was early-onset IBD. One of the symptoms of IEIs such as caspase-8 deficiency is early-onset of IBD. Patients with early-onset had normal T cell count and low or normal immunoglobulin levels with insufficient immune response.

Co-occurrence of celiac disease and glycogen storage disease in a five-year-old patient with diabetes mellitus; a case report.

A patient presented with edema, ascites and jaundice. Histologic report was consistent with Celiac Disease. Liver biopsy commensurate with Glycogen storage disease III, which was confirmed by genetic testing. A gluten-free diet was initiated. After 2 months, ascites was relieved, hepatic function was improved, and hepatic size reduced.

Expression analysis of miRNA-155 level in Helicobacter pylori related inflammation and chronic gastritis.

Background and Objectives: Helicobacter pylori, is a major etiologic agent associated with gastritis. There is more evidence of noncoding microRNAs (miRs) dysregulation in gastrointestinal diseases, including inflammation caused by Helicobacter pylori. Also, the classification of gastrointestinal malignancies using the miRs profile is better than the protein profile. MiRNA-155(miRNA-155) among other miRs plays an important role in control of inflammation and gastric malignancy, so it can be remarkable prognosis marker of gastric cancer in the phase of chronic gastritis. The aim of this study was to compare the expression of miRNA-155 in gastric biopsy and serum samples of adult patients with chronic gastritis. Materials and Methods: Biopsy and blood samples were collected from endoscopy candidates at Taleghani hospital, Tehran, during 2019. H. pylori infection was detected using histology, culture and molecular PCR methods. Based on cagA and vacA genotyping, the toxicity of H. pylori isolates were determined. After RNA extraction, the expression rate of miRNA-155 was evaluated by real-time polymerase chain reaction (RT-PCR) in gastric tissue and serum of adults infected by H. pylori (n = 30) compared with control group without infection (n = 20). RNU6 housekeeping miRNA were used as endogenous control and statistical analyses were performed using SPSS, ANOVA and Student's t-test. Results: miRNA-155 expression in H. pylori infected adult patients increased significantly by 5.61 and 10.11 fold in serum and tissue respectively, compared to that observed in the control group. Evaluation of miRNA-155 expression pattern in relation to bacterial virulence factors showed that the increase in miRNA-155 expression is independent of CagA and VacA toxins. Conclusion: According to the differential expression patterns of miRNA-155 in serum samples of the infected adult patients, miRNA-155 has the potential to evaluate as chronic gastritis marker.

Effects of probiotic supplementation on abdominal pain severity in pediatric patients with irritable bowel syndrome: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Probiotic supplementation has been used to alleviate abdominal pain in children and adolescents with irritable bowel syndrome (IBS), but the evidence is not compelling. Thus, a systematic review and meta-analysis of randomized clinical trials (RCTs) were performed to investigate the effects of probiotic supplementation on abdominal pain in pediatric patients with IBS. METHODS: PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library, and Embase were the available databases searched to find relevant randomized clinical trials up to April 2021. The effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). RESULTS: Seven RCTs with 441 participants were included, from which the meta-analysis demonstrated that probiotic supplementation has a significant effect on reducing abdominal pain in pediatric patients with IBS (WMD = - 2.36; 95% CI - 4.12 to - 0.60; P = 0.009). Although our study involved children and adolescents (≤ 18 years), the effects of probiotic supplementation seem to be more potent in patients under 10 years old (WMD = - 2.55; 95% CI - 2.84 to - 2.27) compared to patients aged 10-18 years (WMD = - 1.70; 95% CI - 2.18 to - 1.22). The length of supplementation longer than four weeks was more effective (WMD = - 2.43; 95% CI - 2.76 to - 2.09). CONCLUSION: Probiotic supplementation can reduce abdominal pain in pediatric patients with IBS.

The association between vitamin D status and inflammatory bowel disease among children and adolescents: A systematic review and meta-analysis.

Aim: Vitamin D deficiency is very common among children with IBD. Since there are conflicting results regarding the association of vitamin D with IBD, we conducted this systematic review to confirm the association of vitamin D with IBD. Methods: We conducted a systematic search in Scopus, Cochrane Library, Web of Science, PubMed, and Google Scholar to find relevant studies. Articles with cross-sectional and case-control designs that reported the association between vitamin D and IBD among children were included. Results: Eventually, 9 studies (with 16 effect sizes) reported the mean and SD or the median and the interquartile range of serum vitamin D levels in both subjects with IBD and control subjects. The random effects meta-analysis revealed that subjects with IBD had -1.159 ng/ml (95% CI: -2.783, 0.464) lower serum vitamin D concentrations compared with their healthy counterparts, but this difference was not significant. A total of 14 studies (with 18 effect sizes) with 2,602 participants provided information for the prevalence of vitamin D deficiency or insufficiency in patients with IBD as 44% (95% CI: 0.34-0.54) with significant heterogeneity noted among studies (p < 0.001; I2 = 97.31%). Conclusion: This systematic and meta-analysis study revealed that vitamin D deficiency was associated with IBD. Longitudinal studies should be conducted in the future to confirm our findings. Large randomized controlled trials assessing the doses of supplementation of vitamin D would provide a better understanding of the association between vitamin D and IBD.

COVID-19 pneumonia in a child with hepatic encephalopathy: A case study.

Coronavirus disease 2019 (COVID-19) is caused by the seventh coronavirus, known as the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Children often have milder diseases than adults with very rare mortality. Gastrointestinal manifestations and a mild increase in liver enzymes have been reported in 8.8% to 53% of COVID-19 cases. However, liver failure is extremely rare and has not been reported so far in the literature. The prevalence of comorbidities is not clear in children with COVID-19. Here, we reported a fatal case of simultaneous pneumonia secondary to SARS-CoV-2and acute liver failure in a 14-year-old boy with liver cirrhosis.

Increased regulatory T cells in peripheral blood of children with eosinophilic esophagitis.

AIM: Considering the allergic basis of Eosinophilic esophagitis (EoE), this study was conducted to evaluate peripheral blood Tregs in children with EoE. BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of gastrointestinal tract. Regulatory T cells (Tregs) have a confirmed role in allergic disorders. METHODS: Children with EoE, gastroesophageal reflux disease (GERD) and healthy controls (HC) (10 subjects in each group) were recruited after diagnosis by a pediatric gastroenterologist and allergist. After obtaining informed written consent, peripheral blood was obtained. Peripheral blood mononuclear cells were isolated by Ficoll gradient centrifugation. Flowcytometry was used to enumerate peripheral blood Tregs (CD4 +CD25 +FOXP3+ gated lymphocytes were considered as Tregs). RESULTS: CD4+ gated lymphocytes significantly increased in EoE and GERD groups compared to HC group (p= 0.018). Tregs also was significantly increased in EoE in comparison to HC group (p=0.016). There were no statistically significant differences in Tregs of EoE as compared to GERD subjects (p=0.085). CONCLUSION: Peripheral blood Tregs increase in patients with EoE as compared to healthy controls, which may be indicative of a feedback mechanism to regulate inflammatory responses.

Diagnostic Challenges in the Early Onset of Inflammatory Bowel Disease: A Case Report.

Inflammatory bowel disease (IBD) with very early onset manifestations (younger than six years of age) is an essential pediatric gastrointestinal disease that encompasses a group of diverse and rare genetic defects. It may be associated with chronicity, premalignant nature, and high morbidity and mortality during childhood. Because of overlapping phenotypes, the definitive diagnosis based on conventional strategies is frequently a challenge. However, many patients with different molecular pathologies are treated with the same therapeutic strategy. In this context, it is essential to define a more reliable method to provide an opportunity for a rapid and accurate diagnosis. Here we report a novel homozygous exonic variant in a patient with an IBD-like lesion in the colon during the infancy period. A 7 months old boy who was born of a consanguineous marriage developed gastrointestinal disorders early in life. After complete diagnostic workups, this case underwent conventional therapy of IBD for five months; but clinical remission was not achieved. We identified a novel homozygous mutation (c.684C>T p(=)) in exon 7 of IL-12RB1 gene that in silico studies indicated its significance in the splicing process. At the 14th month of age, this case died. Our finding reveals the importance of genetic screening as an early diagnostic tool in the identification of the underlying causes of IBD with very early onset manifestations, particularly infantile (< 2 years of age) IBD. This strategy makes an opportunity in prompt diagnosis and targeted therapy.

Assessing the Prevalence and Treatment of Malnutrition in Hospitalized Children in Mofid Children's Hospital During 2015-2016.

BACKGROUND: Malnutrition in hospitalized patients causes problems in treatment and increases hospitalization duration. The aim of this research was to determine the prevalence of malnutrition in hospitalized children. METHODS: Children aged 1 month to 18 years (n = 1186) who were admitted to medical and surgery wards of Mofid children's hospital from November 2015 to February 2016, entered the study. We measured different anthropometric variables in patients with malnutrition. Also, nutritional counseling was performed and three months follow-up was done. RESULTS: Patient data were registered in questionnaires particularly for children 2 years old and less. 597 children under 2 years of age and 607 children over two years entered the study. The data analysis was done by SPSS version 22.0 (Chicago, IL, USA). The t test inferential method was used in comparing variables. P values less than 0.05 were considered statistically significant. Based on the body mass index (BMI) Z score, and in accordance with the World Health Organization (WHO) cut-off, among children over 2 years, 9% were diagnosed as overweight or obese, 54% were within the normal range and 37% were underweight at time of admission. In the underweight group, 43% were mildly, 21.2% were moderately and 35.8% were severely underweight. Based on the weight for length Z score in patients less than 2 years of age at time of admission, 6% were overweight, 60% were in normal range and 34% were underweight. Among children with malnutrition, 21% had mild, 3.0% had moderate and 10% had severe malnutrition. No significant meaningful relation was found between prevalence of malnutrition and severity of illness. In the moderate to severe undernutrition group, nutritionist counseling was done. Comparison of BMI and weight, before and after admission (the baseline and the follow up visits), was done by means of repeated measurements. Comparison of the patient's weight at time of admission with weight at 1, 2 and 3 months after the first nutritional consultation showed statistically meaningful difference (P value < 0.05). CONCLUSION: Growth indices need to be evaluated in every hospitalized child. Nutritional consultation is useful in children with malnutrition. The main purpose of early diagnosis of malnutrition is to prevent its progression, and also to design a useful, applicable and cost-effective nutritional intervention for malnutrition treatment.

Very early onset inflammatory bowel disease: Investigation of the IL-10 signaling pathway in Iranian children.

BACKGROUND & AIM: Comparing to adult inflammatory bowel disease (IBD), those with early onset manifestations have different features in terms of the underlying molecular pathology, the course of disease and the response to therapy. We investigated the IL-10 signaling pathway previously reported as an important cause of infantile (Very Early Onset) IBD to find any possible variants. METHOD: With the next generation sequencing technique we screened IL-10, IL-10RA and IL10RB genes of 15 children affected by very early onset-GI (gastrointestinal) disorders. Additionally, we analyzed them based on Thermo Fisher immune deficiency panel for genes either having a known role in IBD pathogenesis or cause the disorders with overlapping manifestations. We performed multiple functional analyses only for the cases showing variants in IL-10- related genes. RESULT: In 3 out of 15 patients we identified variants including a homozygous and heterozygote mutations in IL-10RA and a novel homozygous mutation in IL-12RB1. Our functional studies reveal that in contrast to the IL-10RA heterozygote mutation that does not have deleterious effects, the homozygous mutation abrogates the IL-10 signaling pathway. CONCLUSION: Our study suggests we need to modify the classical diagnostic approach from functional assays followed by candidate- gene or genes sequencing to the firstly parallel genomic screening followed by functional studies.

Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea.

BACKGROUND: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. METHODS: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. RESULTS: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. CONCLUSIONS: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.

Simultaneous Presentation of Wilson's Disease and Autoimmune Hepatitis; A Case Report and Review of Literature.

INTRODUCTION: Coexistence of Wilson's disease and autoimmune hepatitis has been rarely reported in English literature. In this group of patients, there exist features of both diseases and laboratory and histopathological studies may be misleading. Medical treatment for any of these entities, per se, may result in poor response. Therefore, by considering the acute hepatitis resembling Wilson's disease and autoimmune hepatitis, simultaneous therapy with immunosuppressive and penicillamine may have a superior benefit. CASE PRESENTATION: We present the case of a 10-year-old boy with nausea, vomiting, yellowish discoloration of skin and sclera, abdominal pain and tea-color urine. Physical examination showed mild hepatomegaly and right upper quadrant tenderness. Laboratory and histochemical studies and atomic absorption test were done and the results were highly suggestive of both Wilson's disease and autoimmune hepatitis, in him. CONCLUSIONS: This case study highlights, although rare, the coexistence of Wilson's disease and autoimmune hepatitis and the need to maintain a high level of awareness of this problem. Therefore, it is reasonable to consider this type of hepatitis in rare patients, with dominant features of both diseases at the same time.