Celiac disease (CD) is a common autoimmune disorder characterized by an immune-mediated reaction to gluten. We conducted a survey study of the pediatric gastroenterology list server to assess the practices of North American pediatric gastroenterologists in the management of CD. Overall, 160 out of 2400 respondents participated in the study, of which 52.5% of the respondents were females and 72.5% were practicing in university hospitals. Overall, respondents were practicing in adherence to the latest guidelines, except only 36% were screening for hepatitis B virus immunization at diagnosis on most of the visits, and 25% were utilizing human leukocyte antigens typing on most visits if serologies were negative. In addition, female respondents screened for vitamin D deficiency more often than males with a p value < 0.05.

Juvenile hemochromatosis is a rare inherited disorder of iron regulation leading to iron overload, which usually presents before the age of 30. One of the most serious clinical characteristics associated with early-onset iron overload is liver disease with eventual cirrhosis, often associated with a reduced life expectancy even after treatment. This case report summarizes an asymptomatic pediatric patient with persistently elevated transaminase levels, which led to a diagnosis of juvenile hemochromatosis relatively early in the course of his disease. The aim of this case report is to increase awareness and stress the importance of early diagnosis and treatment, as it is vital to prevent life-threatening complications and optimize patient outcomes. Consideration should be taken to recognize potential manifestations despite the rarity of the condition. Patients with signs of hepatocellular injury without explanation should prompt evaluation including consideration for iron overload after other common causes are ruled out.

Abstract Introduction: Celiac Disease (CD) is a common autoimmune disorder characterized by an immune-mediated reaction to gluten. The aim of the study is: 1. To assess the current practices of pediatric gastroenterologists (GI) in the management of CD; 2. To assess how these responses compare to the current EIEBPG; and 3. To assess how the practices vary based upon geographic location. Methods: This study was a cross-sectional survey of members of the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN). After obtaining NASPGHAN and IRB approval, members (n=2400) were sent a SurveyMonkey® survey consisting of 22 questions of which 17 were based upon the Evidence-Informed Expert Best Practice Guidelines (EIEBPG). Results: A total of 8.3% (198/2400) responders completed the survey. Respondents from North America (NA) comprised the largest group, 80.8% (160/198), followed by 7.6% (15/198) European (EU) responders. When indicated, Human Leukocyte Antigen (HLA) typing was used by 11 (5.6%) responders on all visits. Comparing respondents from NA and EU on the majority of visits, 141/160 (88.1%), 59/160 (36.9%), and 153/160 (95.6%) respondents from NA screened for Vitamin D, Hepatitis B Virus (HBV) immunization, and had access to dietician respectively, compared to 7/15 (46.7%), 2/15 (13.3%), and 9/15 (60%) EU respondents, respectively. Conclusion: Overall, most study respondents were reportedly adhering to EIEBPG. Providers need to utilize HLA typing more for patients with negative serology. EU providers need to be more consistent for screening for vitamin D and there is room for improving access to dietitians of EU celiac disease patient’s clinic visits.

Background and objective Pediatric populations are highly sensitive to ionizing radiations and, therefore, are more at risk of their harmful outcomes. Our study aimed to determine the percentage of children who underwent a CT scan after presenting to the ED with abdominal pain. The secondary aim was to determine the change in management related to the CT results. In addition, we also wanted to determine the predictors associated with the use of abdominal CT scans in the evaluation of children presenting to ED with abdominal pain as well as the predictors associated with positive CT scan results in children with abdominal pain. Materials and methods We retrospectively reviewed the medical records of children with abdominal pain seen in our ED from 01/01/2011 through 12/30/2012. Patients aged 4-18 years presenting with abdominal pain were identified from the medical records. Data on demographics, clinical characteristics, associated factors, CT use, CT findings, and change in management were collected. Data were analyzed using Chi-square (χ2) analysis and Student's t-test. Results A total of 1,780 charts were reviewed and 1,272 children were included in the study. The mean age of the cohort was 12.6 ± 4.6 years; 62.6% were female and 68.7% were African American. Of note, 14% (181/1,272) of the study group had received a CT scan; change in medical management was noted in 34.8% (63/181) of the scanned patients. Predictors of CT use included older age (p<0.0001), male gender (p<0.0001), white race (p<0.0001), an attending without advanced training in pediatric emergencies (p=0.001), acute onset of symptoms (p<0.0001), higher pain score (p<0.0001), right lower quadrant pain (p<0.0001), abdominal wall rebound tenderness (p<0.0001), abdominal tenderness (p<0.0001), fever (p<0.0001), and absence of constipation (p=0.04). Positive CT scan results were predicted by the presence of fever (p=0.013), lack of constipation (p=0.025), and white race (p=0.022). A multivariate analysis could not be done because not all data were available for each patient. Conclusion The use of the CT scan in children with abdominal pain affected the management in one out of three patients (34.8%). Fever, constipation, and white race were the factors associated with an increased likelihood of performing a CT scan and were also linked to positive results.

INTRODUCTION: The aim of the study was to (1) determine if any clinical variables and laboratory values at presentation are predictors of relapse in pediatric UC; (2) To determine the differences in clinical variables and laboratory values for those who relapsed early, compared with who relapsed late. METHODS: Charts were review for all patients ages 1–21years with pediatric ulcerative colitis. Variables studied included: demographic parameters: age at diagnosis, gender, race, BMI percentiles, family history of IBD; presenting symptoms: gross blood in the stool, nocturnal stools, fever & extra-intestinal manifestations; phenotypic characteristics, using the Montreal classification; laboratory data: WBC count, hemoglobin, hematocrit, platelet count, ESR and CRP. Data was analyzed using χ2 test and Student’s t-test. A P-value < 0.05 was considered statistically significant. RESULTS: A total of 28 patients were included. 16 relapsed within first 2 years, >50% relapsed in the first 7months, defined as early relapse. The mean age for all the patients was 11.5 ± 4.8 years, 71.4% were males, and 96.4 % were Caucasians. CONCLUSION: According to our study 57% of the patients relapsed, comparable to other studies. No predictors of relapse between relapse vs. no relapse group and early vs. late relapse were found to be statistically significant.

Introduction Constipation represents 3% of all office visits to pediatricians and 10% - 45% of consultations with pediatric gastroenterologists. It has been reliably established that the role of abdominal x-rays (AXR) in the diagnosis of constipation in pediatrics is limited; yet, significant overdiagnosis of constipation exists when plain abdominal x-rays are used in the acute setting for abdominal pain or to screen for other disorders. This results in loss of time, resources, exposure to unnecessary radiation, and potentially missing the primary diagnosis. The purpose of this study is to determine the sensitivity and specificity of AXR in diagnosing constipation in the acute setting. Objectives To determine 1) the sensitivity and specificity of plain AXR in the diagnosis of constipation and 2) the effect of age, race, gender, comorbid conditions, and practice setting on the diagnosis of constipation. Methods This study was a historical cohort study of children (two to 18 years of age) who were seen at Ascension St. John Children’s Hospital between March 2015 - March 2018 and who had a plain AXR performed during an emergency department (ED) visit or inpatient stay. If AXR results contained keywords, such as “constipation,” “stool load,” “fecal retention,” and “fecal load,” the ambulatory medical record, Athena® (http://www.athenahealth.com), was searched to determine if the child had an ambulatory visit in the ensuing 45 days. Chart review was conducted to assess if the diagnosis of constipation was later confirmed by history and physical examination by a pediatrician or gastroenterologist at that visit. By comparing data from both encounters, the sensitivity and specificity of plain AXR in diagnosing constipation was assessed. All data were analyzed using the Statistical Package for Social Sciences (SPSS), v. 25.0 (IBM SPSS Statistics, Armonk, NY) and a p-value of 0.05 or less was considered to indicate statistical significance. Results Over the three-year study period, 1,383 AXRs were performed on 1,116 patients. The sensitivity of AXR in the diagnosis of constipation was 73.8%, specificity 26.8%, positive predictive value 46.4%, and negative predictive value of 54.3%. Pediatric gastroenterologists were more likely to diagnose constipation (63.2%) compared to pediatricians (41.4%) and pediatric surgeons (33.3%) (p = 0.04). Conclusions AXRs are not a reliable means of diagnosing constipation. Overall, we found similar sensitivity and specificity of AXR in diagnosing constipation compared to previous studies. Yet, our study gives new insight into the practices around diagnosing constipation in a single-center community hospital pediatric acute setting and the radiology department. This further emphasizes the need to review current practices and impart more education both in the acute care setting and radiology department.

INTRODUCTION: Severe iron deficiency among infants and toddlers may rarely lead to protein losing enteropathy due to barrier dysfunction of the enterocyte brush border. We report a case of a child who presented with generalized edema due to protein losing enteropathy associated with severe iron deficiency. CASE DESCRIPTION/METHODS: A 16 months old Asian American female presented with a 3 days history of noticeable pallor and generalized edema without any respiratory distress, bleeding or bruising, prolonged fevers, vomiting, diarrhea and any noticeable change in amount or color of urine. The child’s diet predominantly consisted of dairy. She was pale, edematous, afebrile and hemodynamically stable. She had no hepatosplenomegaly or lymphadenopathy. Her diagnostic work up was consistent with iron deficiency anemia(low Hb of 6g/dL, low MCV and MCHC, low-normal reticulocyte count, low ferritin, low iron saturation and increased iron binding capacity) with normal white blood cell count and slightly elevated platelet count. Hemolytic anemia was ruled out by negative direct Coombs test, negative antibody screen and normal haptoglobin level. She had low albumin level (1.7g/dL) without any evidence of liver dysfunction (normal bilirubin, liver enzymes and coagulation profile) or nephrosis (no proteinuria). Her stool was positive for occult blood and negative for any infection. Celiac disease was excluded by negative anti-tissue transglutaminase IgA antibody and negative anti-gliadin antibody. She received packed red blood cell transfusion and albumin infusion after which her anemia and edema resolved. She underwent upper and lower GI endoscopy with biopsies which showed non-specific inflammation. Her stool alpha-1 antitrypsin was elevated (more than 1.13mg/g) which confirmed protein losing enteropathy associated with severe iron deficiency and hypoalbuminemia. She was started on treatment with an amino acid based formula and high dose oral iron supplements. She improved with the treatment and her symptoms resolved completely. DISCUSSION: Severe iron deficiency may lead to protein losing enteropathy in children. In these cases, patients may present with generalized edema and their diagnosis may be confused with nephrotic syndrome, liver failure, heart failure and lymphangiectasia. Appropriate diagnostic workup confirms the diagnosis. It is treated by limiting dairy intake, use of hypoallergenic formula and iron supplementation.

BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is the presence of chronic hepatic steatosis in the absence of infections, steatogenic medication use, metabolic/genetic disorders, malnutrition, or ethanol consumption. NAFLD encompasses a spectrum of liver damage varying from non-alcoholic fatty liver (NAFL) on the most clinically benign end of the spectrum to cirrhosis on the opposite extreme, where most liver-related morbidity and mortality occurs. CASE REPORT:We report a case of a 9-year-old boy with history of obesity (BMI 32.1 kg/m² – 99th percentile) and non-alcoholic fatty liver disease, who was referred to our pediatric gastroenterology clinic with a 1-week history of vomiting and right upper-quadrant abdominal pain. A review of the past medical history revealed transaminitis for the last 4 years and a dietary regimen for the last 2 years with poor compliance and follow-up. An extensive workup revealed an SGPT of 327 unit/L, SGOT 186 unit/L, and triglycerides of 208 mg/dL; infectious, metabolic, genetic, and autoimmune etiologies were ruled-out. The median liver stiffness measured by Fibroscan was 14 kPa, consistent with F4 fibrosis, and the cap median value was 271 dB/mW, reflective of S2 steatosis. An ultrasound-guided core liver biopsy revealed steatohepatitis with bridging and encircling fibrosis consistent with early/evolving cirrhosis. CONCLUSIONS:Although cirrhosis is rarely seen in pediatric patients with NAFLD, it should always be considered. Secondly, Fibroscan, a non-invasive imaging procedure, is a useful tool to assess the level of fibrosis and steatosis in patients with NAFLD; early evaluation of our patient could potentially have limited the progression to cirrhosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition in children, with a high mortality rate of 41.99%. Often, due to the atypical presentation of HLH, the syndrome is difficult to diagnose. We report a case of an atypical presentation of HLH and the diagnostic dilemma that we faced. An 11-year-old boy was hospitalized with recurrent fever, hepatosplenomegaly, and worsening jaundice. Initial laboratory workup revealed an elevated prothrombin time (PT), high bilirubin, increased alanine transaminase (ALT), and positive Epstein Barr virus (EBV) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) and EBV immunoglobulin G (IgG). Based on our patient's presentation and initial laboratory findings, further extensive workup was done, which revealed cytopenias, hypofibrinogenemia, hemophagocytosis on biopsy, absent natural killer (NK) cell activity, high serum ferritin level, and high soluble CD25 (sIL-2 receptor); a diagnosis of HLH was made. He was started on broad-spectrum antibiotics, antivirals, antifungals, and cyclosporine. He became hypoxic and hypotensive and hence was intubated and started on vasopressors. However, his coagulation profile continued to deteriorate. He started bleeding from multiple sites and became unresponsive to ventilatory support, eventually dying as a result of complications of HLH. The ambiguous clinical presentation makes the diagnosis of this syndrome difficult. However, due to the high fatality rate, early recognition and prompt treatment are of utmost importance.

We report a case of a 17-month-old male with a history of developmental delay with poor muscle control, hepatomegaly, and transaminitis. Ultrasound of abdomen revealed hepatomegaly with a liver span of 13 cm, homogeneous parenchyma, and normal spleen size. Liver and muscle biopsies were obtained: the liver biopsy revealed distended hepatocytes with excessive glycogen accumulation and fine septate fibrosis. Biopsy of the right vastus lateralis muscle showed focal swollen glycogen containing mitochondria. For the developmental delay, a chromosomal microrarray was ordered. The chromosomal microarray revealed the patient to have 1q21 duplication syndrome and 16p11.2 deletion syndrome. Given the liver and muscle biopsy findings, a glycogen storage disease panel was sent which identified the patient to be hemizygous for a variant of uncertain significance denoted as p.Gly 131Val, c.392G > T in the PHKA2 gene. PKHA2 gene encodes the alpha subunit of hepatic phosphorylase kinase. This change in the PHKA2 gene was in a highly conserved region and had been reported in another patient with decreased enzymatic activity of the phosphorylase kinase and who had symptoms of GSD IX. Based on this, the patient was started on treatment for GSD IX, and his family met with a dietician.

Objectives: To assess the effect of long-term (104 weeks) treatment with recombinant sebelipase alpha (rhSA) on serum lipid and hepatic transaminase levels, and liver histopathology in 4 siblings diagnosed with lysosomal acid lipase deficiency (LAL-D). Methods: Four male siblings from the same nonconsanguineous parents were diagnosed with the late-onset phenotype of LAL-D in 2015. Liver specimens were obtained by biopsy at baseline and after 104 weeks of enzyme replacement with rhSA (1 mg/kg, IV, every 2 weeks). Hepatic transaminase, lipid and lipoprotein levels were assessed at baseline and sequentially every 16 weeks for 104 weeks. Hepatic steatosis was evaluated from hematoxylin and eosin-stained specimens, and fibrosis was evaluated (Metavir-scoring system) from trichrome-stained specimens obtained at baseline and following 104 weeks of treatment with rhSA. Results: All 4 siblings had improvement in their serum lipid and hepatic transaminase levels after treatment with rhSA. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from baseline by an average of 47% and 56%, respectively. The fasting triglyceride and low-density lipoprotein cholesterol (LDL-C) levels decreased from baseline by an average of 43% and 60%, respectively. Hepatic steatosis decreased from baseline grade 3 to posttreatment grade 1. Hepatic fibrosis did not advance following 104 weeks of treatment with rhSA and regressed in 1 sibling. Conclusions: Treatment with rhSA for 104 weeks in 4 siblings with LAL-D demonstrated improvement in their hepatic transaminase and serum lipid levels, accompanied by reduction of hepatic steatosis and no progression of fibrosis.

Objective: Rare disease Background: Non-alcoholic fatty liver disease (NAFLD) is the presence of chronic hepatic steatosis in the absence of infections, steatogenic medication use, metabolic/genetic disorders, malnutrition, or ethanol consumption. NAFLD encompasses a spectrum of liver damage varying from non-alcoholic fatty liver (NAFL) on the most clinically benign end of the spectrum to cirrhosis on the opposite extreme, where most liver-related morbidity and mortality occurs. Case Report: We report a case of a 9-year-old boy with history of obesity (BMI 32.1 kg/m(2) - 99th percentile) and non-alcoholic fatty liver disease, who was referred to our pediatric gastroenterology clinic with a 1-week history of vomiting and right upper-quadrant abdominal pain. A review of the past medical history revealed transaminitis for the last 4 years and a dietary regimen for the last 2 years with poor compliance and follow-up. An extensive workup revealed an SGPT of 327 unit/L, SGOT 186 unit/L, and triglycerides of 208 mg/dL; infectious, metabolic, genetic, and autoimmune etiologies were ruled-out. The median liver stiffness measured by Fibroscan was 14 kPa, consistent with F4 fibrosis, and the cap median value was 271 dB/mW, reflective of S2 steatosis. An ultrasound-guided core liver biopsy revealed steatohepatitis with bridging and encircling fibrosis consistent with early/evolving cirrhosis. Conclusions: Although cirrhosis is rarely seen in pediatric patients with NAFLD, it should always be considered. Secondly, Fibroscan, a non-invasive imaging procedure, is a useful tool to assess the level of fibrosis and steatosis in patients with NAFLD; early evaluation of our patient could potentially have limited the progression to cirrhosis.

Introduction Crohn's disease (CD) is an immune-mediated inflammatory bowel disease (IBD) that can affect any portion of the gastrointestinal tract from the mouth to the anus. The clinical course of CD is characterized by periods of symptomatic relapse and remission. Clinical variables may identify a subset of patients with CD at risk for relapse. Identifying these patients, and early stratification-based treatment would be of utmost clinical importance in optimizing the management and is likely to improve long-term disease outcome. In pediatric-onset IBD there is a paucity of data for predicting clinical behavior and results are conflicting. With this background, we hypothesized that routinely measured clinical variables at the time of diagnosis would predict relapse in patients with CD, and sought to investigate the clinical predictors of relapse present at the time of diagnosis in our patient population. We further compared differences in clinical variables and laboratory values for patients who relapsed early, compared with those who relapsed late. Methods We conducted a retrospective chart review of patients diagnosed with CD by clinical, radiological, endoscopic and histological criteria at St. John Providence Children’s Hospital pediatric GI clinic between 01/2006 and 12/2014. Patients were followed until they had their first relapse or for three years from diagnosis, whichever was earlier. Variables studied included demographic factors (age, gender, race, BMI, BMI percentiles and family history of IBD), presenting symptoms (blood in stools, nocturnal stools, fever, and extra-intestinal manifestations), phenotypic characteristics (using Montreal classification), and laboratory data [white blood cell (WBC) count, hemoglobin, hematocrit, platelet count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)]. Results Twenty-nine patients were included in the study. One was lost to follow up, and 28 were included in the analyses. The relapse rate was 50% at three years, and 32% patients relapsed within one year of diagnosis. Low BMI percentile at diagnosis (41.5 ± 28.8 vs. 18.0 ± 20.3; p-value 0.03) was a predictor of relapse. Comparing early relapse to those who relapsed late, there were no statistically significant differences between the two groups. Conclusions Low BMI percentile at presentation was associated with increased risk of relapse, suggesting that routinely measured clinical variables may have role in predicting first relapse in this patient population. There was no significant difference in the variable comparing patients who relapsed early vs. those who relapsed late. Future prospective studies with larger sample sizes need to be done to predict relapse.

Mitochondrial DNA (mtDNA) maintenance defects are a group of diseases caused by deficiency of proteins involved in mtDNA synthesis, mitochondrial nucleotide supply, or mitochondrial dynamics. One of the mtDNA maintenance proteins is MPV17, which is a mitochondrial inner membrane protein involved in importing deoxynucleotides into the mitochondria. In 2006, pathogenic variants in MPV17 were first reported to cause infantile-onset hepatocerebral mtDNA depletion syndrome and Navajo neurohepatopathy. To date, 75 individuals with MPV17-related mtDNA maintenance defect have been reported with 39 different MPV17 pathogenic variants. In this report, we present an additional 25 affected individuals with nine novel MPV17 pathogenic variants. We summarize the clinical features of all 100 affected individuals and review the total 48 MPV17 pathogenic variants. The vast majority of affected individuals presented with an early-onset encephalohepatopathic disease characterized by hepatic and neurological manifestations, failure to thrive, lactic acidemia, and mtDNA depletion detected mainly in liver tissue. Rarely, MPV17 deficiency can cause a late-onset neuromyopathic disease characterized by myopathy and peripheral neuropathy with no or minimal liver involvement. Approximately half of the MPV17 pathogenic variants are missense. A genotype with biallelic missense variants, in particular homozygous p.R50Q, p.P98L, and p.R41Q, can carry a relatively better prognosis.

Dr. Maciejko is a member of the Alexion speaker bureau.

Esophagogastroduodenoscopy (EGD) has become a key element in the diagnosis and therapy of many gastrointestinal diseases affecting children. The aim of this study was to evaluate predictors of positive outcomes in children undergoing their first diagnostic EGD with biopsies at a single center.

We present 4 normal-weight sibling children with lysosomal acid lipase deficiency (LAL-D). LAL-D was considered in the differential diagnosis based on the absence of secondary causes and primary inherited traits for their marked hyperlipidemia, together with unexplained hepatic transaminase elevation. Residual lysosomal acid lipase activity confirmed the diagnosis. DNA sequencing of LIPA indicated that the siblings were compound heterozygotes (c.894G>A and c.428+1G>A). This case describes the unusual occurrence of all offspring from the same nonconsanguineous mother and father inheriting compound heterozygosity of a recessive trait and the identification of an apparently unique LIPA mutation (c.428+1G>A). It highlights the collaborative effort between a lipidologist and gastroenterologist in developing a differential diagnosis leading to the confirmatory diagnosis of this rare, life-threatening disease. With the availability of an effective enzyme replacement therapy (sebelipase alfa), LAL-D should be entertained in the differential diagnosis of children, adolescents, and young adults with idiopathic hyperlipidemia and unexplained hepatic transaminase elevation.

BACKGROUND:Celiac disease (CD) and eosinophilic esophagitis (EoE) are distinct diseases of the gastrointestinal tract with specific clinico-pathological characteristics. Recent studies have found higher rates of EoE in patients with CD than in the general population. Our aim was to estimate the incidence of EoE among children who were diagnosed with CD over a 42-month period.METHODS:The study included patients diagnosed with CD based on endoscopy and histopathological findings between January 2010 and June 2013. Histopathology reports of esophageal biopsies were reviewed to identify all cases of EoE. The patients' presenting symptoms, laboratory evaluations, endoscopic and histopathological findings, treatments, and follow-ups were analysed.RESULTS:Fifty-six patients with CD were identified, of whom six (10.7%) were diagnosed with both CD and EoE. Four of these patients presented with abdominal pain and diarrhea, two presented with failure to thrive, and three presented with food allergies. Endoscopic and histopathological changes typical of EoE were observed in all six patients. During follow-up, two patients showed significant improvement with the gluten-free diet and a proton-pump inhibitor (PPI). Two patients improved with the elimination diet and two patients were treated with topical corticosteroid therapy. Endoscopic appearance was normal in all children on follow-up endoscopy after treatment. Biopsy samples also showed resolution of the histologic features of EoE in all of the children.CONCLUSION:The incidence of EoE in our cohort of children with CD was 10.7%, which is higher than what has been reported for the general population. In all children undergoing upper gastrointestinal endoscopy for suspected CD, coexistence of EoE should be considered.

Studies have suggested that inflammatory bowel diseases (IBD) follow a seasonal pattern with regard to their onset and exacerbations. The aim of this study is to determine if there is any seasonal pattern to the onset and exacerbation of IBD in the pediatric population and if the birth of children diagnosed with IBD follows a seasonal pattern.