Vitamine B12 deficiency in children: a diagnostic challenge.

Cobalamin or vitamin B12 (vitB12) is involved in DNA synthesis, haematopoiesis and myelinisation. Consequently, vitB12 deficiency causes various symptoms, such as megaloblastic anaemia, neurologic signs or pancytopenia. Despite possible severe symptoms, vitB12 deficiency can present asymptomatically. We report six paediatric patients with different aetiologies of vitB12 deficiency ranging from a subtle to a more overt presentation. VitB12 deficiency is a diagnostic challenge due to the lack of consensus on normal values of vitB12 and its co-markers (folate, holotranscobalamin, methylmalonic acid, homocysteine) and the lack in specificity and sensitivity of the serum vitB12 analysis. All cases were treated with parenteral vitB12. Last decades, evidence supporting high dose oral treatment being as effective as the intramuscular (IM) therapy, also in children, is growing.

Not all pediatric intestinal polyps are alike.

BACKGROUND/AIMS: In childhood, clinical presentation of intes- tinal polyps is variable. Painless rectal red blood loss is the most common presenting sign. Most polyps are sporadic, isolated and benign. However, it is important to correctly identify exceptions. Rare inherited polyposis syndromes need to be recognized because of their increased risk of intestinal and extra-intestinal malignancies. Furthermore, a correct diagnosis and treatment of rare gastro-intestinal malignancies is crucial. METHODS: Between 2016 and 2018 we encountered 4 different types of intestinal polyps. A database search was performed and patient files were checked for clinical manifestations and histo- pathology. Literature was searched to recapitulate red flags for these syndromes, probability of underlying genetic disorders and diagnostic criteria. RESULTS: Between 2016 and 2018, 28 patients presented at the Ghent University Hospital with 30 juvenile polyps. Furthermore, we diagnosed juvenile polyposis syndrome, Li Fraumeni syndrome and familial adenomatous polyposis (FAP) in 1 patient each, whilst 2 FAP patients were in follow-up. Each of these diagnoses has a different lifetime risk of (extra)-intestinal malignancy and requires a different approach and follow-up. Histopathology and genetic testing play an important role in identifying these syndromes in pediatric patients. CONCLUSION: Although most intestinal polyps in childhood are benign juvenile polyps that require no follow-up, rare inherited syndromes should be considered and correctly diagnosed since adequate follow-up is necessary to reduce morbidity and mortality from both gastrointestinal and extraintestinal complications and malignancies.

Acid-base disturbances in dehydrated patients with cystic fibrosis : four case reports with review of literature.

Most episodes of vomiting, reduced intake and diarrhoea in children can be evaluated and treated without additional tests. However, when the degree of clinical dehydration is not in line with the patient's medical history, other diagnoses should be suspected. In the presence of a hyponatraemic hypochloraemic metabolic alkalosis, cystic fibrosis (CF) should be included in the differential diagnosis, especially if there is failure to thrive even in the absence of respiratory symptoms. Furthermore, young patients diagnosed with CF have a higher risk for an acute electrolyte decompensation caused by increased salt and fluid losses. We present 4 paediatric cases to raise the awareness of electrolyte disturbances in CF patients.

Hepatitis B virus vaccination and revaccination response in children diagnosed with coeliac disease : a multicentre prospective study.

AIM: This study evaluates hepatitis B virus (HBV) vaccination response in children with celiac disease (CD). Response in initial non-responders after a single booster vaccination as well as factors influencing HBV vaccination response were evaluated. METHODOLOGY: Anti-hepatitis B surface antibodies (a-HBsAB) were checked in all children with CD and a documented complete HBV vaccination. An a-HBsAB <10 U/L was considered as non-response. A single intramuscular HBV-vaccine booster was advised to all non-responders. Response was checked at the next appointment. RESULTS: 133 children with CD were included, median age of 7.3 years (range 1.7-17.3) and 46 (35%) were male. The age at CD diagnosis was 6.0 years (range 1.1-15.7). HBV non-response was documented in 55% (n=73/133). No other factors were influencing the response. A booster was documented in 34/73 (47 %) initial non-responders (3 refused (4%), 36 (49%) had no follow up). Response after booster vaccination resulted in immunity in 22/34 (65%) and persisting non-response in 12/34 (35%). A single booster is able to reduce non-response from 55% (73/133) to 23% (22/94). CONCLUSION: A significantly lower immune response following HBV vaccination in children with CD was confirmed. A single intramuscular booster vaccination is able to induce a serologic response in two thirds of the initial non-responders. Control of HBV vaccination response has to become part of the follow-up in CD patients.

Constipation and fecal incontinence in children with cerebral palsy. Overview of literature and flowchart for a stepwise approach.

BACKGROUND AND STUDY AIMS: Constipation and fecal incontinence are common problems in neurologically impaired children. This paper aims to give an overview on bowel problems in cerebral palsy children and to suggest a stepwise treatment approach. A pubmed search was performed looking at studies during the past 20 years investigating bowel problems in neurologically disabled children. RESULTS: The search revealed 15 articles. Prevalence and presentation was the subject of 8 papers, confirming the importance of the problem in these children. The other papers studied the results of different treatment modalities. No significant differences between treatment modalities could be demonstrated due to small studied cohorts. Therefore, no specific treatment strategy is currently available. An experienced based stepwise approach is proposed starting with normalization of fiber intake. The evaluation of the colon transit time could help in deciding whether desimpaction and eventually laxatives including both osmotic (lactulose, macrogol) as well as stimulant laxatives might be indicated. Or, in case of fast transit loperamide or psyllium can be tried. Surgery should be a last resort option. CONCLUSION: Studies investigating constipation and continence in neurologically impaired children are scarce, making it difficult to choose for the optimal treatment. A stepwise treatment approach is proposed, measuring the colon transit time to guide treatment choices.

Rectal red blood loss in a healthy toddler is not always a juvenile polyp.

Aim Heterotopic gastric mucosa is a well-known congenital anomaly in Meckel's diverticula and duplication cysts. Solitary heterotopic gastric mucosa in the rectum is a rare and frequently overlooked abnormality. Starting from a patient history, the literature is searched and all cases reported over the past 20 years are reviewed and compared to a summary of the older cases. Differences between adult and childhood presentation are outlined and our patient is compared with prior reported cases. Case A 3-year-old girl presented with recurrent rectal blood loss caused by heterotopic gastric mucosa without duplication cyst. She was endoscopically treated with two-stage endoscopic surgical dissection (ESD). Up to now, rectal heterotopic gastric mucosa has been reported in 34 adults and 24 children, including this patient. There is an overall male dominance (69%). Presenting complaints in children were recurrent fresh blood loss per anum (96%), pain (46%), perineal ulcers (25%), diarrhoea (8%) and one patient had an ano-cutaneous fistula. Endoscopy revealed a mucosal elevation with a slightly different aspect (33%), a polyp (42%) and a solitary ulcer (25%). Endoscopy in adults reveals more frequently polyps compared to children. Treatment in childhood is mainly surgical where adults are more frequently treated with endoscopic techniques. Conclusion In a child with recurrent rectal bleeding in good general health, it is important to withhold heterotopic gastric mucosa in the differential diagnosis and take sufficient biopsies during endoscopy.

Calcineurin inhibitors dampen humoral immunity by acting directly on naive B cells.

Calcineurin inhibitors (CNI), used frequently in solid organ transplant patients, are known to inhibit T cell proliferation, but their effect on humoral immunity is far less studied. Total and naive B cells from healthy adult donors were cultured in immunoglobulin (Ig)A- or IgG/IgE-promoting conditions with increasing doses of cyclosporin, tacrolimus, rapamycin or methylprednisolone. The effect on cell number, cell division, plasmablast differentiation and class-switching was tested. To examine the effect on T follicular helper (Tfh) cell differentiation, naive CD4(+) T cells were cultured with interleukin (IL)-12 and titrated immunosuppressive drug (IS) concentrations. Total B cell function was not affected by CNI. However, naive B cell proliferation was inhibited by cyclosporin and both CNI decreased plasmablast differentiation. Both CNI suppressed IgA, whereas only cyclosporin inhibited IgE class-switching. Rapamycin had a strong inhibitory effect on B cell function. Strikingly, methylprednisolone, increased plasmablast differentiation and IgE class-switching from naive B cells. Differentiation of Tfh cells decreased with increasing IS doses. CNI affected humoral immunity directly by suppressing naive B cells. CNI, as well as rapamycin and methylprednisolone, inhibited the in-vitro differentiation of Tfh from naive CD4(+) T cells. In view of its potent suppressive effect on B cell function and Tfh cell differentiation, rapamycin might be an interesting candidate in the management of B cell mediated complications post solid organ transplantation.

Raised immunoglobulin A and circulating T follicular helper cells are linked to the development of food allergy in paediatric liver transplant patients.

BACKGROUND: Post-transplant food allergy (LTFA) is increasingly observed after paediatric liver transplantation (LT). Although the immunopathology of LTFA remains unclear, immunoglobulin (Ig) E seems to be implicated. OBJECTIVE: To study humoral and cellular immunity in paediatric LT patients in search for factors associated with LTFA, and compare with healthy controls (HC) and non-transplant food-allergic children (FA). METHODS: We studied serum Ig levels in 29 LTFA, 43 non-food-allergic LT patients (LTnoFA), 21 FA patients and 36 HC. Serum-specific IgA and IgE against common food allergens in LTFA, IgA1 , IgA2 and joining-chain-containing polymeric IgA (pIgA) were measured. Peripheral blood mononuclear cells were analysed by flow cytometry for B and T cell populations of interest. RESULTS: Serum IgA and specific IgA were higher in LTFA compared to LTnoFA. LTFA patients had the highest proportion of circulating T follicular helper cells (cTfh). The percentage of cTfh correlated positively with serum IgA. Unique in LTFA was also the significant increase in serum markers of mucosal IgA and the decrease in the Th17 subset of CXCR5(-) CD4(+) cells compared to HC. Both LT patients exhibited a rise in IgA(+) memory B cells and plasmablasts compared to HC and FA. CONCLUSIONS: LT has an impact on humoral immunity, remarkably in those patients developing FA. The increase in serum markers of mucosal IgA, food allergen-specific IgA and cTfh cells observed in LTFA, point towards a disturbance in intestinal immune homoeostasis in this patient group.

Gastrostomy use in children: a 3-year single centre experience.

AIM: Monocentric retrospective paediatric study describing indications for gastrostomy and major complications, compared to literature data as part of a quality check. METHODS: Records of all gastrostomy patients consulting at the UZ Ghent paediatric gastro-enterology department between January 2007-December 2009 were reviewed in December 2010 regarding indication, age and weight at tube insertion, insertion method, major complications and current gastrostomy tube type. RESULTS: 178 patients were included of which 165 (93%) were placed using the endoscopic pull technique, the others were placed surgically (n = 13). Neurodevelopmental disability with oral motor dysfunction was the major indication (113, 63%). Other indications were failure to thrive due to concomitant disease (65, 37%). Median age at tube insertion was 3yr (interquartile range (IQR) 0.6-9) with median tube time of 3.9 yr (IQR 1.9-7.2). Immediate complications were 1 peritonitis and 1 post-insertion fever episode. Late complications (10, 5.6%) were 1 gastrocolic fistula, 1 dislocation and 8 buried bumpers after 4 yr (range 35-10.4) of tube insertion. The incidence of buried bumper increased significantly with increasing PEG tube time (P < 0.01). Gastro-oesophageal reflux disease (GORD) led to Nissen fundoplication in 45 (25.3%) patients. The proportion of patients receiving a fundoplication remained about 20% over time but the time lapse between the 2 procedures decreased significantly. CONCLUSION: The development of buried bumper is associated to prolonged PEG tube use. In case of important GORD laparoscopic Nissen procedure and PEG placement can be performed simultaneously without increasing complication rate.

Achromobacter xylosoxidans induced bronchiolitis obliterans in cystic fibrosis.

We report a 12-year-old boy with progressive bronchiolitis obliterans caused by Achromobacter xylosoxidans (Ax) colonization after liver transplantation, resulting in a steep decline in lung function.

Meso-Rex shunt using deep femoral vein conduit: first report.

The Meso-Rex shunt (MRS) procedure was first described in 1992 by de VILLE et al. for the treatment of extrahepatic portal vein obstruction (EHPVO) in paediatric liver transplant patients. This technique provides more physiological relief of portal hypertension compared to the porto-systemic shunts, which can lead to long-term complications such as hyperammonaemia and hepato-pulmonary syndrome. Different conduits as autologous and cryopreserved veins or prosthetic grafts have been previously reported. We present herein the first case of a MRS using the autologous deep femoral vein in a 17-year-old female patient affected by EHPVO from unknown reasons.

Anal canal duplication in an 11-year-old-child.

Anal canal duplication (ACD) is the least frequent digestive duplication. Symptoms are often absent but tend to increase with age. Recognition is, however, important as almost half of the patients with ACD have concomitant malformations. We present the clinical history of an eleven-year-old girl with ACD followed by a review of symptoms, diagnosis, treatment, and prognosis based on all the reported cases in English literature.

[Colon transit time in children and young adults with open spinal dysraphism]. / Temps du transit colique chez l'enfant atteint de dysraphisme ouvert.

INTRODUCTION: Patients with open spinal dysraphism (OSD) frequently present constipation and incontinence requiring treatment. AIM: Evaluation of colon transit time (CTT) in patients with OSD, in relation to neural lesion, mobility, bowel habits, and continence status. METHODS: OSD patients aged between 6 and 20 years, who did not use antegrade enemas, were invited to participate in the study. Data from the medical file and information retrieved by questionnaires for constipation and incontinence were collected. The control group consisted of 13 healthy age-matched children. CTT was measured using the 6-day pellet method with an abdominal X-ray on day 7. Laxatives were continued and retrograde colon enemas were stopped 48h prior the X-ray. RESULTS: Thirty of the 33 patients who met the inclusion criteria agreed to participate. Twelve (40%) patients were constipated (Rome III criteria) despite treatment. Fifteen (50%) were continent, with or without treatment. Total CTT was significantly longer in OSD patients (median CTT: 86.4h vs. 43.2h controls). Constipated OSD patients had a significantly prolonged CTT compared to non-constipated patients (CTT: 125.4h vs. 51.6h). Spontaneous continent OSD patients had a normal CTT (CTT: 33.6h). An abnormal CTT predicted the necessity of treatment to achieve continence (P<0.006). CONCLUSION: CTT in OSD patients is significantly prolonged, indicating a neurogenic involvement of the bowel and a slow transit constipation. An abnormal CTT predicts the necessity of therapy to achieve fecal continence.

Colon enemas for fecal incontinence in patients with spina bifida.

PURPOSE: We studied the use of colon enemas in achieving fecal pseudocontinence in patients with spina bifida to define the variables associated with success. MATERIALS AND METHODS: Questionnaires were individually filled out by all patients with spina bifida using colon enemas at our Spina Bifida Reference Center between October 2009 and June 2010. Patient age, type of enema, volume required, evacuation time, followup, continence and independence were recorded. Fecal pseudocontinence was defined as no involuntary stool loss during the last 6 months. Social continence was defined as involuntary stool loss less than once monthly. Children are routinely seen at the reference center, while adults are seen on request. RESULTS: A total of 25 children and 15 adults with spina bifida were studied. Median volume required was 1 liter (range 0.5 to 2) in children and 1.5 liters (0.75 to 3) in adults. Median evacuation time was 30 minutes (range 15 to 60) in children and 60 minutes (30 to 120) in adults. Fecal continence was achieved in 76% of children (19 of 25) and 60% of adults (9 of 15), and social continence in 88% of children (23 of 25) and 67% of adults (10 of 15). A significant relation was found between medical followup since childhood and fecal pseudocontinence. No enema determinants predicted pseudocontinence. CONCLUSIONS: Colon enemas are a valuable method in achieving continence. At our center medical followup from childhood to adulthood is associated with successful acquisition of fecal pseudocontinence.

Serum protein N-glycosylation in paediatric non-alcoholic fatty liver disease.

OBJECTIVE: We have previously shown the potential of glycomics to distinguish patients with steatosis from patients with non-alcoholic steatohepatitis (NASH) in an adult population. The pattern of disease in paediatric patients is distinct from adults. The objective of this study was to characterize the N -glycomic profile of children with varying degrees of non-alcoholic fatty liver disease (NAFLD) and identify potential biomarker profiles of disease. METHODS: Serum protein N-glycosylation patterns of 51 paediatric NAFLD patients were assessed with deoxyribonucleic acid sequencer-assisted fluorophore-assisted capillary electrophoresis and compared with histology. RESULTS: Peak 1 (NGA2F) is the most significantly elevated N-glycan in paediatric NASH patients with peak 5 (NA2) demonstrating the largest decrease. The logarithmically transformed ratio of peak 1 to peak 5 was -0.85 (standard deviation [SD] 0.22) in patients with steatosis and borderline NASH and -0.73 (SD 0.12) in NASH (P = 0.02). The biomarker correlated well with the amount of lobular inflammation with a consistent increase of marker score in ascending stage of lobular inflammation. There was also a trend in differentiating patients with significant fibrosis ≥F2; -0.74 (SD 0.13) from patients with no/minimal fibrosis

Acute pancreatitis complicated with choledochal duct rupture.

Recurrent acute pancreatitis is a rare clinical entity in childhood with unknown incidence (Rosendahl et al., 2007) and often occurring in a familial context. Genetic factors such as PRSS1 mutations (cationic trypsinogen gene) can be found in some patients. However, many remain idiopathic. The natural history remains poorly documented and the most frequent complications reported are pain, exocrine pancreatic insufficiency, diabetes mellitus, and pancreatic adenocarcinoma after long-standing hereditary pancreatitis. We describe a patient with hereditary pancreatitis in whom a mild pancreatitis episode was complicated by a perforation of the ductus choledochus.

Gastric dysmotility following orthopaedic scoliosis surgery in patients with cerebral palsy: a case series.

Scoliosis is a common complication in children with cerebral palsy (CP). In these patients, surgical correction carries a high risk of complications. CP is also associated with gastrointestinal dysmotility such as delayed gastric emptying and gastro-oesophageal reflux. We describe 5 patients with CP in whom symptoms of gastric dysmotility clearly exacerbated after orthopaedic scoliosis surgery. They all showed persisting vomiting, nausea, bloating, weight loss, and anorexia necessitating total parental nutrition and/or jejunal feeding. This intensified nutritional support resulted in weight gain. Symptoms, however, persisted in half of the patients. The aetiology of these gastro-intestinal motility problems following scoliosis surgery remains unclear. Mechanical obstruction needs to be ruled out. Delayed gastric emptying may be due to postprandial antral hypomotility as a consequence of sympathic stimulation. Malnutrition could further aggravate gastrointestinal dysmotility. This complication should be taken into account when surgery for spinal deformities in CP patients is planned, especially in patients with pre-existing gastrointestinal motility problems.

Epstein-Barr virus related lymphoma in inflammatory bowel disease.

Epstein-Barr virus (EBV) induced lymphoproliferative disease is a well-known, feared complication of EBV primo-infection in children treated with immunomodulators or immunosuppressive drugs, eg after transplantation. As the incidence of inflammatory bowel disease (IBD) in young children is rising, more young EBV naive patients are treated with immunomodulatory agents. It is not yet clear whether these patients carry the same risk as transplanted patients to develop lymphoproliferative disease and if so, whether their evolution is comparable. We present the history of a young patient with Crohn's disease who developed an EBV related lymphoma shortly after the primo-infection while being treated with azathioprine. This case argues for a rigorous follow up of young IBD patients treated with immune suppressive drugs, also regarding EBV status.

Long-term assessment of the seal provided by root-end filling materials in large cavities through capillary flow porometry.

AIM: To evaluate the long-term sealing ability of a variety of materials when used as root-end fillings. METHODOLOGY: A total of 140 standardized horizontal bovine root sections (external diameter: 7 mm, height: 3 mm; internal diameter: 2.5 mm) were divided into seven groups, filled with either gutta-percha with AH26, Ketac Fil, Fuji IX, Tooth-Colored MTA, IRM, Ketac Fil with conditioner or Fuji IX with conditioner and submitted to capillary flow porometry at 1 and 6 months to assess minimum, mean flow and maximum pore diameters. Results of the different materials and results by material were analysed statistically using non-parametric tests; the level of significance was set at 0.05. RESULTS: There were no significant differences between the minimum pore diameters associated with the materials at each time. At 1 month the mean flow pore diameters of Ketac Fil were significantly larger than those of gutta-percha, Ketac Fil with conditioner, Fuji IX with conditioner and IRM. There were significant differences between the maximum pore diameters at 1 month (all>IRM; Fuji IX>gutta-percha, Ketac Fil with conditioner, Fuji IX with conditioner) and 6 months (Fuji IX>gutta-percha, IRM; Ketac Fil>gutta-percha, IRM). There were significant differences in the minimum pore diameters between the different points in time for each material except IRM, in the mean flow pore diameters for each material and in the maximum pore diameters for each material except MTA. CONCLUSIONS: All materials were associated with capillary flow. IRM root-end fillings had through pores that were smaller than those associated with other materials. Conventionally setting glass-ionomer cements had the largest pores, although dentine conditioning improved their performance. The seal of all materials improved after 6 months.

Longitudinal study on microleakage of three root-end filling materials by the fluid transport method and by capillary flow porometry.

AIM: (i) To compare the root-end sealing ability of IRM Caps (IRM), Fuji IX Capsules (Fuji IX) and Pro Root MTA Tooth-Coloured Formula (MTA) in teeth obtained from cadavers. (ii) Further research on leakage study methodology by means of comparison of the fluid transport method (FTM) and capillary flow porometry (CFP). METHODOLOGY: Root canal treatment was performed on 33 cadaver teeth in situ 2 weeks prior to root resection and ultrasonic retropreparation (S12/90 degrees D-tip on Suni-Max), after which the teeth were retrieved from the cadavers. Two teeth were kept as positive and negative controls. The other teeth were divided in three different groups at random, with each group receiving one of the retrofill materials. Retrofills were exposed to water 5 min after placement. The teeth were stored at 37 degrees C for 12 h after which the root filling was removed. Microleakage (L in microL day(-1)) was measured for 24 h under a pressure of 1.2 atm using FTM and recorded as L = 0, 0 < L < or = 10, L > 10. The measurements were repeated after 1 and 6 months. After 6 months, leakage was also assessed by CFP in order to measure through pores and their diameters. Results were analysed statistically using nonparametric Kruskal-Wallis and Mann-Whitney U-tests, and Spearman correlation coefficients between the results of both methods were calculated. The level of significance was set at 0.05. RESULTS: (i) A statistically significant difference could be demonstrated between Fuji IX and IRM at 1 month with FTM. FTM revealed a significant difference between Fuji IX and the other materials at 6 months, whereas CFP did not. However, using both methods, Fuji IX showed the best result. (ii) When comparing both techniques, CFP demonstrated through pores in all teeth, whereas with FTM in only 14 of the 31 teeth could through pores be demonstrated. A positive correlation between both methods was demonstrated. CONCLUSIONS: Under the conditions of this study (i) the conventionally setting glass-ionomer cement Fuji IX showed the best results when used as a root-end material and (ii) CFP appeared to be a useful method for leakage evaluation of through pores in endodontics.