Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.

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RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), NOP10, NHP2, and GAR1. Mutations inDKC1,NOP10, orNHP2cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition. Here, we report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males withDKC1p.Glu206Lys and two children with homozygousNOP10p.Thr16Met. Females with heterozygousDKC1p.Glu206Lys developed cataracts and sensorineural deafness, but nephrotic syndrome in only one case of skewed X-inactivation. We found telomere attrition in both pedigrees, but no mucocutaneous abnormalities suggestive of DC. Both mutations fall at the dyskerin–NOP10 binding interface in a region distinct from those implicated in DC, impair the dyskerin–NOP10 interaction, and disrupt the catalytic pseudouridylation site. Accordingly, we found reduced pseudouridine levels in the ribosomal RNA (rRNA) of the patients. Zebrafishdkc1mutants recapitulate the human phenotype and show reduced 18S pseudouridylation, ribosomal dysregulation, and a cell-cycle defect in the absence of telomere attrition. We therefore propose that this human disorder is the consequence of defective snoRNP pseudouridylation and ribosomal dysfunction.

Using pH indicators to measure nasogastric tube aspirate is subjective. Accuracy relies on the reproducibility of results. Colour of solution tested and method of use could also affect the results. This in-vitro study aimed to assess the effect of these variables on the reliability of pH indicators. 250 non buffered fluids (140 clear, 110 coloured) were assessed. pH was measured by 1 rater with 10 pH indicators and compared against values from a calibrated pH meter. 100 samples were tested twice with each indicator. In the first test the solution was dropped onto the indicator. In the second the indicator was immersed in the solution. 100 samples were tested twice (same method) at 2 separate intervals. Pearson's correlation coefficient of the samples compared with those from the pH meter, and the % paired samples in agreement per method of testing and test-retest are shown below.

Background Congenital chloride diarrhea (CLD) is a rare autosomal recessive disease caused by the mutation in member 3 of the solute carrier 26 (SLC26A3). The phenotypic expression is a life-long severe watery Chloride rich diarrhea. Anecdotal association with inflammatory bowel disease (IBD) has been reported suggesting that underlying molecular mechanisms could represent part of an evolving association between IBD and channelopathies. We aimed to investigate this association in a cohort of CLD pediatric patients. Methods A European-based call for cases was made in CLD patients followed up in five different countries. A case report form for each patient was then completed. Results A total of 74 patients with CLD with a range of different CLD mutations were enrolled in the study. Twelve patients of 64 (16%) demonstrated colonic inflammation and were finally diagnosed with IBD: 8 patients with Crohn’s Disease, 2 with Ulcerative Colitis, and 2 IBD-like colitis (IBD-U). The diagnosis was made at a median of 12 years old (IQR: 6–30). Patients had different ethnicities (7 European, 2 Middle East, 1 North Africa, 1 Pakistan, 1 Central Africa). Among the 12 IBD, 2 had a 5-ASA-based treatment, 3 required immunosuppressant and 6 had biologics (Infliximab, Adalimumab and Vedolizumab). Three patients underwent surgery for ileostomy formation for CD that was non-responsive to multiple line of biologics (anti-TNF and anti-integrin): one had colectomy the remnant two colon preservation. Clinical characteristics, such as premature delivery, low weight at birth, fecal Cl- at diagnosis and amount of Cl- supplementation (mmol/kg) did not differ between patients with or without IBD. All patients underwent genotyping for CLD diagnosis and we did not find any specific genetic mutation linked to the development of IBD. Conclusion Sixteen percent of patients enrolled with CLD in our cohort developed IBD. Despite different presentations (CD, UC, IBD-U) all patients had colonic without ileal/small bowel involvement, in line with preliminary murine models of CLD demonstrating a role of colonic mucous layer in the development of colonic inflammation (Xiao et al Acta Physiol Oxf Engl 2014; 211:161–175). Patients’ IBD treatment included a wide range with variable success. Patients with IBD did not differ in their clinical characteristics or genetic mutations compared with non-IBD CLD patients. The role of genetic variants outside the CLD-gene and the microbiome in this association are under investigation.

Gastrointestinal dysmotility is a common problem in a subgroup of children with intestinal failure (IF), including short bowel syndrome (SBS) and pediatric intestinal pseudo-obstruction (PIPO). It contributes significantly to the increased morbidity and decreased quality of life in this patient population. Impaired gastrointestinal (GI) motility in IF arises from either loss of GI function due to the primary disorder (e.g., neuropathic or myopathic disorder in the PIPO syndrome) and/or a critical reduction in gut mass. Abnormalities of the anatomy, enteric hormone secretion and neural supply in IF can result in rapid transit, ineffective antegrade peristalsis, delayed gastric emptying or gastroesophageal reflux. Understanding the underlying pathophysiologic mechanism(s) of the enteric dysmotility in IF helps us to plan an appropriate diagnostic workup and apply individually tailored nutritional and pharmacological management, which might ultimately lead to an overall improvement in the quality of life and increase in enteral tolerance. In this review, we have focused on the pathogenesis of GI dysmotility in children with IF, as well as the management and treatment options.

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Community nurses employed and trained to a high level of competency by a commercial homecare company conducted a further audit of NGT replacement using the NPSA guidance on gastric aspirate pH as the basis of their practice. A rigorous clinical governance programme underpins this activity including regular reassessment of competencies. All nurses recorded their cases prospectively using an in house audit system for 4 months from April, 2015. A total of 23 nurses undertook 181 NGT replacements (children 121; adults 60) in 74 patients (children 60; adults 14). These included 36 (20%) unplanned replacements (children 20/121[16.5%]; adults 16/60 [27%] P¼0.11 NS). The replacement settings were: home 160; nursing home 6; care home 7; respite care 1; school 5; child minders' care 2. The majority of children (75%) were under the age of 5 years. The specific risk assessment tool was used in 100% of cases and led to deferred replacement in 3 patients. There was 1 referral for CXR following failure to obtain a satisfactory pH immediately on discharge from hospital and before commencement of feeding. CXR demonstrated bronchial placement thereby avoiding a "never event". Despite concomitant acid suppressing treatments in many, gastric aspirates were found to have mean pH 3.08. An equivocal pH 5-6 gastric aspirate was found in only 11/181 (6%) but all yielded a pH<5.5 on later retesting with confirmation by a second competent observer. No CXR was requested for failure to obtain a satisfactory pH in accordance with NPSA recommendations. Failed replacement required hospital referral on 2 occasions (1%). Community NGT replacement can therefore be safely and successfully undertaken by appropriately trained nurses in accordance with NPSA guidance without recourse to expensive urgent returns to hospital for radiological assessment e which does not guarantee avoidance of "never events" of which none have occurred following 555 replacements in 227 patients in our 2 audits. References [1] Reducing the harm caused by misplaced nasogastric feeding tubes in adults, children and infants. National Patient Safety Agency; 2011 at www. nrls.npsa.nhs.uk/resources/type/alerts. [2] Cron N. Complete Nutrition 2016;16:50e2. Enteral Feeding and patient safety.