The frequency of Duchenne muscular dystrophy/Becker muscular dystrophy and Pompe disease in children with isolated transaminase elevation: results from the observational VICTORIA study.

Introduction: Elevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia. Methods: This multi-center, prospective study enrolled patients aged 3-216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels >2× the upper limit of normal (ULN) for ≥3 months. Patients with a known history of liver or muscle disease or physical examination findings suggestive of liver disease were excluded. Patients were screened for creatinine phosphokinase (CPK) levels, and molecular genetic tests for DMD/BMD in male patients and enzyme analysis for PD in male and female patients with elevated CPK levels were performed. Genetic analyses confirmed PD. Demographic, clinical, and laboratory characteristics of the patients were analyzed. Results: Overall, 589 patients [66.8% male, mean age of 63.4 months (standard deviation: 60.5)] were included. In total, 251 patients (188 male and 63 female) had CPK levels above the ULN. Of the patients assessed, 47% (85/182) of male patients were diagnosed with DMD/BMD and 1% (3/228) of male and female patients were diagnosed with PD. The median ALT, AST, and CPK levels were statistically significantly higher, and the questioned neurological symptoms and previously unnoticed examination findings were more common in DMD/BMD patients than those without DMD/BMD or PD (p < 0.001). Discussion: Questioning neurological symptoms, conducting a complete physical examination, and testing for CPK levels in patients with isolated hypertransaminasemia will prevent costly and time-consuming investigations for liver diseases and will lead to the diagnosis of occult neuromuscular diseases. Trial Registration: Clinicaltrials.gov NCT04120168.

Management of Gastrointestinal Foreign Bodies with Brief Review of the Guidelines.

Foreign body (FB) ingestion is a common health problem that affects children more than adults. According to gastroenterologists' guidelines, the management of FB ingestion differs slightly between adult and children. This review aimed to compile adult and children guidelines and establish an understandable association to reveal the requirements and timing of the endoscopic procedure, which is the most effective and least complicated technique for gastrointestinal FBs. Coins, pins, and chicken and fish bones have been the most commonly ingested FBs. However, with their increasing use in recent years, large batteries with lithium-ion conversion, stronger magnets composed of rare earth metals, such as neodymium, and superabsorbent objects have become the most morbid and mortal, necessitating new management strategies. Although the approach to gastrointestinal FBs is controversial, with different treatment options available in different disciplines, many studies have demonstrated the efficacy and safety of endoscopic procedures. Many factors influence the timing of endoscopy, including the nature, size, and location of the ingested object and the patient's clinical condition.

A Comparison Between Rome III and Rome IV Criteria in Children with Chronic Abdominal Pain: A Prospective Observational Cohort Study.

BACKGROUND: The Rome IV includes a redefinition of functional gastrointestinal disorders and diagnostic criteria. The present study aimed to compare the Rome III and Rome IV classification results and to reveal their differences in children with chronic abdominal pain. METHODS: The present study is a prospective observational cohort study. Three hundred forty-four children, who were admitted to the pediatric gastroenterology clinic, had abdominal pain for more than 2 months, and were not diagnosed with an organic disease, were included in our study. RESULTS: In children with chronic abdominal pain, Rome IV criteria did not cause a change in the number of patients diagnosed with functional abdominal pain disorders according to Rome III (89.8% vs 89.2%, P >.05). Functional abdominal pain and functional abdominal pain syndrome were the most common diagnoses in Rome III and functional abdominal pain, not otherwise specified in Rome IV. When compared to Rome III, while the diagnosis of functional dyspepsia increased in Rome IV, irritable bowel syndrome decreased. CONCLUSION: In children with chronic abdominal pain, Rome IV criteria did not cause a change in the number of patients diagnosed with functional abdominal pain disorders according to Rome III, but it caused a diagnostic shift. It was seen that some of the children diagnosed with irritable bowel syndrome in Rome III shifted to functional dyspepsia diagnosis in Rome IV.

Possible relationship between refractory celiac disease and malignancies.

Celiac disease (CeD) is a chronic autoimmune disorder that is triggered by gluten in genetically susceptible individuals, and that is characterized by CeD-specific antibodies, HLA-DQ2 and/or HLA-DQ8 haplotypes, enteropathy and different clinical pictures related to many organs. Intestinal lymphoma may develop as a result of refractory CeD. If a patient diagnosed with CeD is symptomatic despite a strict gluten-free diet for at least 12 months, and does not improve with severe villous atrophy, refractory CeD can be considered present. The second of the two types of refractory CeD has abnormal monoclonal intraepithelial lymphocytes and can be considered as pre-lymphoma, and the next picture that will emerge is enteropathy-associated T-cell lymphoma. This manuscript addresses "CeD and malignancies" through a review of current literature and guidelines.

Can a Synbiotic Supplementation Contribute to Decreasing Anti-Tissue Transglutaminase Levels in Children with Potential Celiac Disease?

PURPOSE: Synbiotics can alleviate some intestinal pathologies or prevent trigger mechanisms for some diseases such as celiac disease (CD). If patients with high levels of anti-tissue transglutaminase (anti-tTG) immunoglobulin A (IgA) antibodies have normal duodenal histology, they are followed as potential CD patients. The aim of this study was to investigate the effect of synbiotic use on the blood levels of anti-tTG antibodies in children. METHODS: Eighty-two patients with high anti-tTG levels were included in this study. Patients were randomly divided into two groups. The synbiotic group was treated with a daily dose of a synbiotic including multi-strain probiotics for 20 days. The control group was not administered any medication. Anti-tTG values at baseline and repeat measurements and the percentage change in anti-tTG levels between groups were compared. RESULTS: The anti-tTG level at baseline was 36 U/mL (interquartile range [IQR], 26.4-68 U/mL) in the synbiotic group, and it decreased significantly to 13 U/mL (IQR, 6.5-27.5 U/mL) after 20 days (p<0.05). The anti-tTG level at baseline was 46 U/mL (IQR, 31-89 U/mL) in the control group, which also decreased significantly to 23 U/mL (IQR, 7-41 U/mL) after 20 days (p<0.05). Anti-tTG levels exhibited 73% and 56% decreases in the synbiotic and control groups, respectively (p<0.05). CONCLUSION: It may be speculated that a synbiotic supplementation can contribute to decreasing anti-tTG levels in children with potential CD.

A Case Series of Ingested Open Safety Pin Removal Using a Proposed Endoscopic Removal Technique Algorithm.

PURPOSE: Safety pin ingestion is common in some regions of the world and may lead to severe morbidity and mortality. The aim of this study was to present some practical suggestions for ingested safety pins using an accompanying algorithm, presented for the first time in the literature to the best of our knowledge. METHODS: Twenty children with ingested safety pins during a 4-year period were retrospectively included in the study. RESULTS: Median age of patients was 9.5 months (interquartile range, 6.3-14 months), and 70% were girls. On endoscopic examination, safety pins were observed in the stomach (25%), duodenal bulb (20%), upper esophagus (15%), middle esophagus (10%), and second part of the duodenum (10%) but were not observed in 20% of the cases. Safety pins were removed using endoscopy in 15 cases (75%). In four cases (20%), no safety pin was observed on endoscopic examination. In one case (5%) involving a 6-month-old infant, the safety pin could not be removed although it was observed using endoscopy. No surgical intervention was needed for any patient. No complications such as perforation or deaths developed, except for erosions, due to the foreign body removal procedure. CONCLUSION: Safety pins are easily removed endoscopically. The best option is to remove the safety pin using endoscopy while it is still in the esophagus and stomach. For this reason, endoscopic procedures should be performed as soon as possible in children who have ingested safety pins.

Novel PLVAP Mutation in Protein Losing Enteropathy.

Introduction: A genetic cause of the protein-losing enteropathy (PLE) disease Diarrhea 10 (DIAR10) are mutations in the recently described PLVAP (plasmalemma vesicle protein). Case report: An infant with fatal PLE had a novel homozygous frameshift mutation (c.339dupT; p.Ala114Cysfs*9) leading to a premature stop codon in exon 1 of the PLVAP (NM_031310) gene detected by Whole Exome Sequencing (WES). Conclusion: The frameshift mutation (PLVAP; c.339dupT; p.Ala114Cysfs*9) we have described in our patient has not been previously reported. This is the fifth case reported with a mutation in PLVAP associated with PLE and DIAR10.

The Frequency of Lysosomal Acid Lipase Deficiency in Children With Unexplained Liver Disease.

OBJECTIVES: Evidence suggests that lysosomal acid lipase deficiency (LAL-D) is often underdiagnosed because symptoms may be nonspecific. We aimed to investigate the prevalence of LAL-D in children with unexplained liver disease and to identify demographic and clinical features with a prospective, multicenter, cross-sectional study. METHODS: Patients (aged 3 months-18 years) who had unexplained transaminase elevation, unexplained hepatomegaly or hepatosplenomegaly, obesity-unrelated liver steatosis, biopsy-proven cryptogenic fibrosis and cirrhosis, or liver transplantation for cryptogenic cirrhosis were enrolled. A Web-based electronic data collection system was used. LAL activity (nmol/punch/h) was measured using the dried blood spot method and classified as LAL-D (<0.02), intermediate (0.02-0.37) or normal (> 0.37). A second dried blood spot sample was obtained from patients with intermediate LAL activity for confirmation of the result. RESULTS: A total of 810 children (median age 5.6 years) from 795 families were enrolled. The reasons for enrollment were unexplained transaminase elevation (62%), unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%), cryptogenic fibrosis and cirrhosis (6%), and liver transplantation for cryptogenic cirrhosis (<1%). LAL activity was normal in 634 (78%) and intermediate in 174 (21%) patients. LAL-D was identified in 2 siblings aged 15 and 6 years born to unrelated parents. Dyslipidemia, liver steatosis, and mild increase in aminotransferases were common features in these patients. Moreover, the 15-year-old patient showed growth failure and microvesicular steatosis, portal inflammation, and bridging fibrosis in the liver biopsy. Based on 795 families, 2 siblings in the same family were identified as LAL-D cases, making the prevalence of LAL-D in this study population, 0.1% (0.125%-0.606%). In the repeated measurement (76/174), LAL activity remained at the intermediate level in 38 patients. CONCLUSIONS: Overall, the frequency of LAL-D patients in this study (0.1%) suggests that LAL-D seems to be rare even in the selected high-risk population.

A comparison of the effects of thymoquinone, silymarin and N-acetylcysteine in an experimental hepatotoxicity.

This study investigated the effects of thymoquinone, silymarin, and N-acetylcysteine in a rat model with carbon tetrachloride (CCl4)-induced hepatotoxicity. Although numerous similar studies are available, we aimed to compare the efficacy of these agents by considering N-acetylcysteine as a reference compound. A total of 50 male Wistar albino rats were randomly designated as 5 groups: Group I, CCl4; group II, thymoquinone and CCl4; group III, silymarin and CCl4; group IV, N-acetylcysteine and CCl4; group V, control group. CCl4 was administered intraperitoneally at a dose of 1.5 mL/kg (a mixture of CCl4: olive oil, 1:2) twice a week. Thymoquinone was administered at a dose of 10 mg/kg, silymarin was administered at a dose of 100 mg/kg, and N-acetylcysteine was administered at a dose of 100 mg/kg by daily intraperitoneal injection. At the end of four weeks, blood and liver tests were analyzed. The results were evaluated statistically via the one-way ANOVA test. A p-value <0.05 was considered statistically significant. Thymoquinone, silymarin, and N-acetylcysteine improved the levels of alanine aminotransferase, tumor necrosis factor-α, platelet-derived growth factor-BB, and interleukin-6, which were increased by CCl4. Thymoquinone and silymarin showed the positive increase in liver glutathione levels. Thymoquinone, silymarin, and N-acetylcysteine improved blood total oxidant status. In the histological examinations of liver tissue, thymoquinone decreased necrosis, and inflammation. The most positive decrease in the α-smooth muscle actin-stained hepatic stellate cell count was only observed with thymoquinone. These findings suggest that thymoquinone, silymarin, and N-acetylcysteine have potential for the treatment of diseases causing liver injury. Among these agents, thymoquinone showed the best results on most of the parameters. Since TQ appears to be at least as effective as SM and NAC in our in-vitro study, we propose that it is time for clinical studies with thymoquinone on hepatotoxicity.

A pediatric case of Fascioliasis with eosinophilic pneumonia.

Fasciolia spp. are common trematode infestations worldwide. Fasciolia spp. may lead to hepatic diseases in the acute phase and may cause biliary diseases in the chronic phase. In addition, Fasciolia spp. may rarely cause extrahepatic signs and symptoms. The clinical manifestations of fascioliasis are divided into three groups: typical, atypical, and ectopic. Eosinophilic pneumonia is an atypical presentation of acute fascioliasis and it has been reported very rarely. Herein, we report a boy with marked blood eosinophilia and eosinophilic pneumonia who was diagnosed with fascioliasis by serologic tests and abdominal USG. The patient recovered completely following triclabendazole treatment.

Epidemiology of hepatitis E virus in children in the province of Van, Turkey.

Aim: Hepatitis E virus is an etiological agent of hepatitis which is transmitted enterically and may lead to water-born outbreaks. Although it is mainly transmitted by the fecal-oral route, it is estimated that many cases are associated with zoonotic transmission in developing countries. In this study, we aimed to investigate the seroprevalence of hepatitis E in the childhood age group in the province of Van and to demonstrate the relationship between seroprevalence and demographic properties, residential house/region, water supply used at home, dealing with livestock and history of surgery. Material and Methods: In this study, hepatitis E virus IgG antibody was studied by ELISA method in children aged between 2 months and 18 years between June 2014 and September 2014 in the province of Van. Results: A total of 408 children and adolescents were enrolled in the study. Hepatitis E IgG was found to be positive in 4.2% of the subjects. 179 (43.8%) of the subjects were female and 229 (56.2%) were male. The mean age was 123 months±56.6 months (minimum 2 months, maximum 214 months). When the seropositivity rates were compared by age groups and gender, no difference was found. No correlation was found between hepatitis E seropositivity and the variables of residence, dealing with livestock and water resources. No correlation was found between anti-hepatits E virus seropositivity and parental education level, number of cohabitants and history of surgery. Conclusion: In our study, hepatitis E virus seropositivity was found to be lower compared to the mean seropositivity in Turkey. Hepatitis E infection does not constitute a serious problem in children in the province of Van in accordance with the results reported from different parts of our country. Livestock dealing and usage of well water are not considered risk factors for Hepatitis E infection.

Prevalence of Celiac Disease in Children With Iron Deficiency Anemia in Van Lake Region of Turkey.

We aimed to determine the prevalence of celiac disease (CD) in children with iron deficiency anemia (IDA) and compare the hematological variables of these children with those with IDA, but not with CD. A total of 250 patients aged 1 to 16 years with IDA were included. Upper gastrointestinal system endoscopy was recommended to the patients who were serologically positive for CD. According to the endoscopic biopsy results of 12 patients who have positive screening tests (57.1%), Marsh grade II histopathologic findings were detected in 1 (4.8%) and Marsh grade III histopathologic findings were detected in 11 (52%). The hemoglobin, hematocrit, iron, and ferritin levels were significantly lower in patients with CD with IDA, compared with those with IDA, but not with CD. According to Marsh classification, the percentage of Marsh grade IIIc was found to be higher than the other Marsh grades. As the Marsh grading increased, hemoglobin, hematocrit, serum iron, and ferritin levels decreased and tissue transglutaminase Ig A levels increased. Our results show that CD should be kept in mind as the underlying etiologic factor in patients with IDA.

Prevalence of Helicobacter pylori in children in eastern Turkey and molecular typing of isolates.

The objectives of the present study were to determine Helicobacter pylori via culture, polymerase chain reaction and histopathological diagnosis in 101 children ranging in age from 4 to 18 years, to identify the association among restriction fragment length polymorphism types and clinical disease and to investigate the relationships among different isolates of H. pylori in different age groups. We observed a high prevalence of H. pylori infections in children between the ages of 13 and 18 (75.8%), while children aged 4 to 6 years had the lowest prevalence of infection (40%). H. pylori was detected in 30.7% (31 of 101), 66.3% (67 of 101) and 63.2% (60 of 95) of children as determined by culture methods, PCR and histological examination, respectively. H. pylori isolates with RFLP types I and III were the most common among children with antral nodularity, whereas RFLP types II and IV were the least detected types. Interestingly, all isolates from peptic ulcer patients were type III. Although our results show a high prevalence of H. pylori infections in the pediatric population in eastern Turkey, no association was identified between H. pylori infection with antral nodularity and recurring abdominal pain. In addition, we found low genetic variation among H. pylori isolates from children and no association between RFLP types and antral nodularity (p > 0.05). Additionally, we found that H. pylori isolates with specific RFLP types were predominant in different age groups.

Prevalence of Helicobacter pylori in children in eastern Turkey and molecular typing of isolates

The objectives of the present study were to determine Helicobacter pylori via culture, polymerase chain reaction and histopathological diagnosis in 101 children ranging in age from 4 to 18 years, to identify the association among restriction fragment length polymorphism types and clinical disease and to investigate the relationships among different isolates of H. pylori in different age groups. We observed a high prevalence of H. pylori infections in children between the ages of 13 and 18 (75.8%), while children aged 4 to 6 years had the lowest prevalence of infection (40%). H. pylori was detected in 30.7% (31 of 101), 66.3% (67 of 101) and 63.2% (60 of 95) of children as determined by culture methods, PCR and histological examination, respectively. H. pylori isolates with RFLP types I and III were the most common among children with antral nodularity, whereas RFLP types II and IV were the least detected types. Interestingly, all isolates from peptic ulcer patients were type III. Although our results show a high prevalence of H. pylori infections in the pediatric population in eastern Turkey, no association was identified between H. pylori infection with antral nodularity and recurring abdominal pain. In addition, we found low genetic variation among H. pylori isolates from children and no association between RFLP types and antral nodularity (p > 0.05). Additionally, we found that H. pylori isolates with specific RFLP types were predominant in different age groups.

Gastrointestinal system lesions in children due to the ingestion of alkali and acid corrosive substances.

BACKGROUND/AIM: TO examine esophageal and gastric lesions in children due to the ingestion of alkali and acid corrosive substances and to emphasize all related complications. MATERIALS AND METHODS: The reports of 103 children who ingested or were suspected to have ingested corrosive substances and who then underwent upper gastrointestinal endoscopic inspections were evaluated retrospectively. RESULTS: Of the patients, the mean age was 41 ± 3.6 months, and 57.3% were male. Vomiting was the most common symptom (44.7%). Eighteen different commercial products were defined as corrosive substances: 59.2% of them were alkali, 39.8% were acids, and 1% had a neutral pH. These corrosive agents most frequently contained sodium hydroxide, followed by hydrochloric acid, sodium hypochlorite, and sulfuric acid. Endoscopic inspections were abnormal in 68% of the cases. Esophageal lesions were observed in 56.3% of the patients, while gastric lesions were observed in 35%. During the follow-up period, esophageal strictures developed in 4.9% of patients, while gastric outlet obstructions developed in 1%. CONCLUSION: Of the patients, the mean age was 41 ± 3.6 months, and 57.3% were male. Vomiting was the most common symptom (44.7%). Eighteen different commercial products were defined as corrosive substances: 59.2% of them were alkali, 39.8% were acids, and 1% had a neutral pH. These corrosive agents most frequently contained sodium hydroxide, followed by hydrochloric acid, sodium hypochlorite, and sulfuric acid. Endoscopic inspections were abnormal in 68% of the cases. Esophageal lesions were observed in 56.3% of the patients, while gastric lesions were observed in 35%. During the follow-up period, esophageal strictures developed in 4.9% of patients, while gastric outlet obstructions developed in 1%.

The importance of the serum quantitative levels of hepatitis B surface antigen and hepatitis B e antigen in children with chronic hepatitis B.

BACKGROUND/AIMS: We aimed to investigate the clinical importance of quantitative levels of serum hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), and to detect their correlation with hepatitis B virus (HBV) DNA load, alanine aminotransferase (ALT) levels, hepatic activity index (HAI) and fibrosis scores. MATERIALS AND METHODS: A total of 56 HBeAg-positive children with chronic hepatitis B (CHB) were included in the study. Quantification of HBsAg and HBeAg was performed using an automated chemiluminescent microparticle immunoassay. Comparisons were performed using the paired t-test, Mann-Whitney U test or t-test for independent samples. Correlations were tested using the Pearson correlation analysis. RESULTS: Significant differences were found between groups of pre- and post treatment quantitative levels of HBsAg, HBeAg, HBV DNA, and ALT. Comparison of HBsAg, HBeAg, HBV DNA, and ALT levels before the treatment and decrease ratios of these levels after treatment according to HAI and fibrosis scores did not show any statistically significant differences. There was a positive correlation between pretreatment HBV DNA load and HBeAg levels, and a negative correlation between pretreatment HBV DNA and ALT levels. There was a negative correlation between decrease ratios of HBsAg and ALT levels after treatment. Patients with post treatment HBeAg seroconversion had a lower post treatment HBV DNA load and a higher decrease ratio of HBsAg than patients who did not have HBeAg seroconversion. CONCLUSION: The present study indicated that HBsAg and HBeAg levels significantly decreased during treatment and that HBeAg correlated with HBV DNA load. Quantitative HBeAg and HBsAg assays could therefore have an important role in treatment of CHB.

Assessment of cardiac functions in infants with cow's milk allergy.

BACKGROUND: Cow's milk allergy is the most common food allergy in children, with rates estimated at 1.9% to 4.9%. Clinical phenotypes of cow's milk allergy are varied and involve 1 or more target organs, with the main targets being the skin, respiratory system, and gastrointestinal tract. To date, no studies have investigated detailed cardiac function in children with cow's milk allergy. The current study aimed to investigate cardiac function in infants with cow's milk allergy. MATERIAL/METHODS: We studied 42 infants with cow's milk allergy and 30 age- and sex-matched healthy subjects. Cardiac functions were evaluated by M-mode, pulsed-wave, and tissue Doppler echocardiography. RESULTS: There were no significant differences in ejection fraction or mitral and tricuspid annular plane systolic excursion between the 2 groups. Pulsed-wave Doppler-derived E/A ratios in mitral and tricuspid valves were similar in both groups. Ea/Aa ratios in the left ventricle posterior wall and right ventricle free wall were lower in patients with cow's milk allergy than in the control group. The E/Ea ratio in the left ventricle, isovolumic relaxation time, deceleration time, and right and left ventricular myocardial performance indices were higher in patients in the study group. CONCLUSIONS: Our study identified reduced early diastolic tissue Doppler velocities in infants with cow's milk allergy.

Auditory p300 event-related potentials in children with Sydenham's chorea.

UNLABELLED: P300 event-related potentials (ERPs), objective measures related to cognitive processing, have not been studied in Sydenham's chorea (SC) patients. PURPOSE: To assess cognitive impairment with P300 ERPs. METHOD: Seventeen patients with SC and 20 unaffected healthy children were included. Stanford-Binet test was used for psychometric assessment, and odd-ball paradigm was used for auditory ERPs. RESULTS: There was no significant difference in P300 latencies between the SC-pretreatment group, SC-posttreatment group and control group (p>0.05). Mean interpeak latencies in SC-pretreatment group and SC-posttreatment group showed significant prolongation compared with the control group (p<0.05). Mean interpeak latencies in SC-posttreatment group were significantly decreased compared with SC-pretreatment group (p<0.05). Compared to controls, patients did not show significant difference in Stanford-Binet intelligence examination. CONCLUSION: This report suggests that interpeak latencies and amplitudes of P300 ERPs could be useful for detecting and monitoring cognitive impairment in SC patients.