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.

Background: The most common cause of intestinal failure (IF) in childhood remains short bowel syndrome (SBS), where bowel mass is significantly reduced due to a congenital atresia or resection and parenteral nutrition (PN) needed. Home PN has improved outcome and quality of life, but the long-term therapeutic goal is to achieve enteral autonomy whilst avoiding long term complications. This paper is aimed at discussing nutritional strategies available to clinicians caring for these patients. Methods: A literature search was performed from 1992 to 2022 using Pubmed, MEDLINE and Cochrane Database of Systematic Reviews, and recent guidelines were reviewed. In the absence of evidence, recommendations reflect the authors’ expert opinion. Results: Consensus on the best possible way of feeding children with IF-SBS is lacking and practice varies widely between centres. Feeding should commence as soon as possible following surgery. Oral feeding is the preferred route and breast milk (BM) the first milk of choice in infants. Donor BM, standard preterm or term formula are alternatives in the absence of maternal BM. Extensively hydrolysed or amino acid-based feeds are used when these are not tolerated. Solids should be introduced as soon as clinically appropriate. Children are encouraged to eat by mouth and experience different tastes and textures to avoid oral aversion. Aggressive weaning of PN and tube (over-) feeding are now discouraged. Conclusions: To date, uniform agreement on the optimal type of feed, timing of food introduction and feeding regime used is lacking and great difference in practice remains. There is need for more research to establish common treatment protocols.

Basidiobolomycosis is a rare fungal disease caused by Basidiobolus ranarum. Involvement of the gastrointestinal tract is unusual and poses both a diagnostic and therapeutic challenge, as clinical signs are non-specific and predisposing risk factors are lacking. It can mimick inflammatory bowel disease, primary immunodeficiency, or a malignancy and should be considered in patients who do not respond to standard therapy. We present the case of a 22 months old boy with confirmed colonic Basidiobolomycosis, who presented with severe eosinophilic inflammation of the gastrointestinal tract. Panfungal PCR performed on DNA extracted directly from a tissue sample confirmed the presence of Basidiobolus. He made a full recovery with a combination of surgery and prolonged targeted antifungal medication.

Parenteral Nutrition (PN) is prescribed to children with intestinal failure. Although life saving, complications are common. Recommendations for indications and constituents of PN are made in the 2005 guidelines by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). The aim of this study was to establish if the indications for prescribing PN in a tertiary children’s hospital were appropriate, and to identify complications encountered. Data were compared to those published by the National Confidential Enquiry into patient outcome and death (NCEPOD) carried out in the United Kingdom in 2010. Children and newborns receiving inpatient PN over a 6 months period were entered into the study and data was collected prospectively. The appropriate indications for the use of PN were based on the ESPGHAN guidelines. Recorded complications were divided into metabolic, central venous catheter (CVC) related, hepatobiliary and nutritional. A total of 303 children (67 newborns) were entered into the study. The main indications for the start of PN were critical illness (66/303), surgery (63/303) and bone marrow transplantation (28/303). The ESPGHAN recommendations were followed in 91.7% (278/303) of cases (95.5% of newborns, 90.7% of children). PN was considered inappropriate in 12/303 patients and equivocal in 13. The mean PN duration was 18 days (1–160) and the incidence of complications correlated to the length of PN prescribed. Metabolic, hepatobiliary and CVC related complications affected 74.6, 24.4, 16.4% of newborns and 76.7, 37.7 and 24.6% of children respectively. In relation to the appropriate indications for the start of PN our results mirrored those reported by the NCEPOD audit (92.4% of newborns and 88.6% children). However, the incidence of metabolic disturbances was higher in our cohort (74.6% vs 30.4% in children, 76.7% vs 14.3% in newborns) but CVC related complications lower amongst our newborns (16,4% vs 25%). Although the indications for inpatient PN in children is mostly justified, there is still a proportion who is receiving PN unnecessarily. PN related complications remain common. There is a need for better education amongst health professionals prescribing PN and access to nutritional support teams to reduce unwanted side effects.

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.

Congenital diarrhoeas and enteropathies (CODE) are a heterogeneous group of disorders. Many affected infants present with catastrophic dehydration in the first few days of life, although the clinical phenotype is variable. Advances in the understanding of underlying pathomechanisms and genetic testing, as well as improved management, in particular intravenous nutrition support, have allowed affected patients to survive well beyond childhood. Awareness and understanding of these rare diseases are hence needed, both amongst paediatricians and adult physicians. In this review, we discuss the different groups of disorders based on a review of the current literature and provide a diagnostic and therapeutic approach. Many of the subtypes of CODE result in the need for prolonged or indefinite parenteral nutrition. Further research is needed to identify new CODE to improve the recognition and management of these children, which can assist in developing new targeted therapies and potentially a long-term cure.