Microvillus Inclusion Disease Caused by MYO5B: Different Presentation and Phenotypes Despite Same Mutation.

Microvillus inclusion disease (MVID) is associated with specific variants in the MYO5B gene causing disrupt epithelial cell polarity. MVID may present at birth with intestinal symptoms or with extraintestinal symptoms later in childhood. We present 3 patients, of whom 2 are siblings, with MYO5B variants and different clinical manifestations, ranging from isolated intestinal disease to intestinal disease combined with cholestatic liver disease, predominant cholestatic liver disease clinically similar to low-gamma-glutamyl transferase PFIC, seizures, and fractures. We identified 1 previously unreported MYO5B variant and 2 known pathogenic variants and discuss genotype-phenotype correlations of these variants. We conclude that MVID may present phenotypically different and mimic other severe diseases. We suggest that genetic testing is included early during diagnostic investigations of children with gastrointestinal and cholestatic presentation.

Safety of High-Volume Plasmapheresis in Children With Acute Liver Failure.

OBJECTIVES: Paediatric acute liver failure (P-ALF) is a rare condition and is associated with a high mortality rate. Management of P-ALF aims to stabilise vital organ functions and to remove circulating toxins and provide vital plasma factors that are lacking. High-volume plasmapheresis (HVP) removes protein-bound substances and improves survival in adult ALF. It is unknown if this effect can be extrapolated to P-ALF. The aim of this study is to report the safety and feasibility of HVP in P-ALF. METHODS: Children with P-ALF were offered HVP if bilirubin was higher than 200 µmol/L or if the aetiology was toxic hepatitis. HVP was performed with fresh frozen plasma corresponding to 10% of the body weight on a minimum of 3 consecutive days. Diagnostics, biochemical and clinical data during HVP as well as outcome data after 3 months were collected from 2012 to 2019 and retrospectively analysed. RESULTS: Sixteen children were treated by HVP and completed at least one series of three treatment sessions with HVP. The only complication seen was an increase in pH > 7.55 in three children within the first 12 hours and was corrected with hydrochloric acid. No bleeding or septic episodes were noted during HVP. Eight children survived without liver transplantation, two survived after successful grafting and a total of six children died. The liver injury unit score between survivors with their own liver and the rest, the two groups was significantly different (P = 0.005). CONCLUSION: HVP with fresh frozen plasma is feasible and well tolerated in children with P-ALF. No serious adverse events and no procedure-related mortality were observed.

Stability and resilience of the intestinal microbiota in children in daycare - a 12 month cohort study.

BACKGROUND: We performed a 12-month cohort study of the stability and resilience of the intestinal microbiota of healthy children in daycare in Denmark in relation to diarrheal events and exposure to known risk factors for gastrointestinal health such as travelling and antibiotic use. In addition, we analyzed how gut microbiota recover from such exposures. RESULTS: We monitored 32 children in daycare aged 1-6 years. Fecal samples were submitted every second month during a one-year observational period. Information regarding exposures and diarrheal episodes was obtained through questionnaires. Bacterial communities were identified using 16S rRNA gene sequencing. The core microbiota (mean abundance > 95%) dominated the intestinal microbiota, and none of the tested exposures (diarrheal events, travel, antibiotic use) were associated with decreases in the relative abundance of the core microbiota. Samples exhibited lower intra-individual variation than inter-individual variation. Half of all the variation between samples was explained by which child a sample originated from. Age explained 7.6-9.6% of the variation, while traveling, diarrheal events, and antibiotic use explained minor parts of the beta diversity. We found an age-dependent increase of alpha diversity in children aged 1-3 years, and while diarrheal events caused a decrease in alpha diversity, a recovery time of 40-45 days was observed. Among children having had a diarrheal event, we observed a 10x higher relative abundance of Prevotella. After travelling, a higher abundance of two Bacteroides species and 40% less Lachnospiraceae were seen. Antibiotic use did not correlate with changes in the abundance of any bacteria. CONCLUSION: We present data showing that Danish children in daycare have stable intestinal microbiota, resilient to the exposures investigated. An early age-dependent increase in the diversity was demonstrated. Diarrheal episodes decreased alpha diversity with an estimated recovery time of 40-45 days.

Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities?

Background: Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. Methods: In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. Results: We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Conclusion: Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.

Dientamoeba fragilis, a Commensal in Children in Danish Day Care Centers.

Dientamoeba fragilis is an intestinal protozoan of debated clinical significance. Here, we present cross-sectional and longitudinal observations on D. fragilis in children aged 0 to 6 years from a 1-year multi-day-care-center cohort study set in Copenhagen, Denmark. The inclusion period for the cohort was 2009 through 2012. Stool samples collected from the children were accompanied by questionnaires completed by the parents or guardians of the children. Using real-time PCR, D. fragilis was detected in the first stool sample from 97 of 142 (68.3%) children. We evaluated the associations between seven plausible risk factors (age, sex, having siblings, having domestic animals at home, having had infant colic, recent history of intake of antibiotics, and recent history of travel abroad) as well as six reported symptoms (lack of appetite, nausea, vomiting, abdominal pain, weight loss, and diarrhea) and testing positive for D. fragilis The final multivariable model identified being >3 years old and having a history of recent travel abroad as risk factors for testing positive for D. fragilis Moreover, univariable analyses indicated that having siblings was a risk factor. There was no statistical association between a recent history of gastrointestinal symptoms and testing positive for D. fragilis Among the 108 children who were represented by ≥2 samples and thus included in the longitudinal analysis, 32 tested negative on the first sample and positive later, and the last sample from each of the 108 children was positive. The results are in support of D. fragilis being a common enteric commensal in this population.

[Oedematous malnutrition can also be seen in Danish children].

We describe two children with oedematous malnutrition; one admitted to a nutrition unit in Uganda and another to a paediatric department in Denmark. Both children received nutritional therapy and recovered. Although oedematous malnutrition is rarely seen in industrialized countries, the condition has been associated with chronic diseases. It is a life-threatening condition, and the pathogenesis remains unknown. Specialized nutrition products have been developed for low-resource clinics in developing countries, however, no specific protocols or products are available for physicians in Denmark.

Childhood diarrhoea in Danish day care centres could be associated with infant colic, low birthweight and antibiotics.

AIM: Diarrhoea is very common in children attending day care centres. The aim of this study was to examine certain predisposing risk factors for an association with diarrhoea, including foreign travel, treatment with antibiotics, having household pets, infant colic, bottle feeding, using a pacifier and low birthweight. METHODS: A dynamic one-year follow-up cohort study comprising 179 children from 36 day care centres was conducted from September 2009 to July 2013 in Copenhagen, Denmark. Questionnaires were sent to the children's parents or legal guardians every two months for a year, requesting information on gastrointestinal symptoms and exposure. A logistic regression was performed to identify the odds ratios of different risk factors for diarrhoea. RESULTS: The odds ratios for diarrhoea were 1.97 (0.93-4.20) for children with a history of infant colic, 1.91 (0.90-4.04) for low birthweight children and 1.45 (0.74-2.82) for children who had used antibiotics. Having a pet in the household had a possible protective effect towards diarrhoeal events, with an odds ratio of 0.47 (0.20-1.09). CONCLUSION: A history of infant colic, low birthweight, and to a lesser extent antibiotic use, possibly increased the risk of diarrhoea in Danish children in day care centres.