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.

The incidence of EoE did not increase between 2001 and 2006. Onset of symptoms did not vary by season, indicating that allergens triggering EoE are present all year around. Vomiting and feeding disorders are seen in young children, while dysphagia and heartburn are seen in older children. As endoscopic findings were normal in 50 % of cases, an esophageal biopsy should be performed in all patients with suspected EoE.

Our objectives were to determine the prevalence of biliary dyskinesia (BD) as an indication for cholecystectomy in children and to identify presenting clinical findings and optimal ejection fraction (EF) associated with the resolution of symptoms after surgery. We conducted a retrospective review of medical records of 212 pediatric patients who underwent cholecystectomy from August, 1998 to November, 2006. Patients who met criteria for BD had their short-term outcomes examined by record review and their long-term postoperative outcomes recorded by questionnaire. To compare EF and clinical presentation to symptom resolution or outcome, χ tests were used. Logistic regression was used to evaluate possible predictors of symptom resolution. BD was the indication for cholecystectomy in 20% of patients (44 of 212). Short-term outcome was not predicted by any of the collected variables. An EF ≤11% predicted higher rate of symptom resolution (P=0.02). Although patients with specific right upper quadrant pain had higher rates of long-term improvement than those with nonspecific abdominal pain (57.9% vs. 18.2%), this did not reach significance (P=0.057). The only predictor emerging from the logistic regression was EF cutoff at 11% (odds ratio=17.5; 95% confidence interval, 1.756-174.418). In this series, symptoms of BD were more likely to be resolved by cholecystectomy in children with EF ≤11%.

BackgroundCeliac 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.MethodsThe 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.ResultsFifty-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.ConclusionThe 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.

BackgroundPolyethylene Glycol 3350 (Miralax®) without electrolytes is commonly used for 3–4 days as bowel preparation for colonoscopy in children. One-day preparation has been anecdotally reported to be effective but there are few published prospective studies comparing the safety and efficacy of one-day preparation with that of three-day preparation. This study was conducted to compare the efficacy and safety of a one-day bowel preparation with Miralax® with that of a three-day preparation for colonoscopy in children.MethodsWe conducted a prospective, randomized controlled trial with children age 2–21 yrs. undergoing elective colonoscopy. Patients were randomly assigned to receive Miralax® for either one or three days. Children with known electrolyte disturbances, dehydration, fecal impaction, metabolic or renal disease were excluded. A metabolic panel was monitored before and after bowel preparation. Subjects reported the tolerability and side effects of Miralax® via a survey. Effectiveness of the bowel preparation was assessed using a stool diary and a bowel cleansing scale during colonoscopy.Results32 subjects were enrolled; 18 received one-day bowel preparation and 14 received 3-day preparation. There were no differences between the groups in efficacy of bowel preparation based on colonoscopic grading or the safety of the preparation. One-day preparation was as well tolerated as three-day preparation.ConclusionMiralax® used one day as bowel preparation for elective colonoscopy in children is safe, effective and well tolerated. Physicians should consider offering a one-day option for bowel preparation, which would allow children to miss fewer days of school prior to colonoscopy.Trial registrationTrial Registration Number: NCT02174497. Date of Registration: 02 May, 2014 URL of register: clinicaltrials.gov.

BackgroundEsophagogastroduodenoscopy (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.ResultsThis retrospective study was based on findings from existing EGD and histopathological reports. All procedures were performed between July 2006 and July 2013. Details of each patient’s clinical presentation and EGD were abstracted from medical records to determine the predictors of positive EGD outcomes. A total of 1133 records of patients between the ages of 0 and 18 years old were evaluated. Of these patients, 51.5% (n = 573) were female and 24.5% (n = 278) were younger than 4 years old. The mean age at the time of EGD was 9.6 ± 5.7 years (mean ± standard deviation). The most common indications for the procedure were abdominal pain (54.9%) and emesis (31.9%). The overall prevalence of any endoscopic abnormality was 54.5% and the overall prevalence of any histological abnormality was 59.1%. A multivariate logistic regression found that patients 12 years or older (odds ratio, OR = 1.46; 95% confidence interval, CI 1.31–1.63), African–American race (OR = 2.20; 95% CI 1.45–3.34), dysphagia (OR = 1.96; 95% CI 1.28–3.00) and positive celiac antibodies (OR = 2.25; 95% CI 1.52–3.34) were all significant independent predictors of a positive EGD outcome.ConclusionsSeveral clinical variables were found to be independent predictors of positive EGD outcomes in children and adolescents. Prospective studies using standardized definitions of clinical variables and endoscopy outcomes are needed to further understand predictors of positive EGDs.

In vitro cell culture studies of bone marrow and peripheral blood progenitor cells from patients with juvenile myclomonocytic leukemia (JMML) consistently show spontaneous proliferation and selective hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). This GM-CSF hypersensitivity dose-response assay has become a component of the international diagnostic criteria for JMML. The authors report a 2-week-old boy with perinatal human herpesvirus 6 (HHV-6) infection in whom in vitro bone marrow culture studies suggested the diagnosis of JMML by showing increased spontaneous proliferation, inhibition of this growth by anti-GM-CSF antibodies, and hypersensitivity to GM-CSF. Polymerase chain reaction viral studies from whole blood DNA and the shell vial viral culture assay were both positive for HHV-6. The patient's condition improved with expectant treatment, with an eventual return to normal blood counts and resolution of hepatosplenomegaly. This case of perinatal HHV-6 infection shows that viruses can initially mimic the in vitro culture results found in patients with JMML. It also illustrates that patients suspected of having JMML should be observed if there are no signs of progressive disease and concurrent features suggestive of viral infection.

Background/Aims: Early weaning has been shown to induce intestinal ornithine decarboxylase (ODC) activities and cell proliferation in rats. No information is available about the effect of early weaning on ODC activity in the stomach. Methods: Suckling rats were prematurely weaned on postnatal day 15 and followed through day 21. Oxyntic gland mucosa of stomach was obtained on postnatal days 15, 16, 18 and 21 (days 0, 1, 3 and 6 after early weaning) and assayed for ODC activity, DNA, protein and pepsinogen activity. α-Difluoromethyl ornithine (DFMO), a specific ODC inhibitor, was given orally to early-weaned pups and its resultant effects were assessed on days 1 and 6 after early weaning. Results: Stomach mucosal wet weight, DNA, protein and pepsinogen activities significantly increased on day 6 after early weaning. ODC activity increased on days 1, 3, and 6 after early weaning, with the highest increase (3-fold) on day 1 when compared to controls. The increases of ODC activity, DNA and protein contents as induced by early weaning were significantly suppressed when pups were exposed to DFMO. However, no suppression of pepsinogen activity was observed. Conclusions: Our study shows that early weaning induces ODC activity and functional growth in the stomach. Gastric ODC activity is essential in gastric mucosal growth processes but not in differentiation. The induction of stomach ODC may act as an early marker in the growth of stomach mucosa induced by early weaning in rats.