{
  "abstract": "Niemann-Pick C (NPC) is a neurovisceral lysosomal disorder resulting from autosomal recessive inheritance of pathogenic variants in NPC1 or NPC2. The clinical association of NPC and inflammatory bowel disease (IBD) has been recognised over the last twenty years but remains poorly understood. While IBD clinically expressed as Crohn’s disease (CD) is the predominant form and hypothesis of impaired autophagy and immune dysregulation as the underlying mechanism, identification and management of these patients remains unclear. We present a case series of five paediatric patients from a single UK metabolic centre who had IBD associated with NPC.We conducted a retrospective review of patients from a single metabolic centre with a dual diagnosis of IBD and NPC. We reviewed biochemical, radiological and endoscopic results. We reviewed the clinical course of this cohort, both from a neurological and gastrointestinal perspective.We identified five patients with NPC and IBD. All 5 patients were female, with mean age at diagnosis of IBD 6.2 (range 2-11y). NPC diagnosis preceded IBD in four patients by a mean of 4.6y (range 2-6y) at a mean age of 2.8y (4m-7y). All had typical NPC presentation with splenomegaly +/- hepatomegaly +/- jaundice. Neurological features emerged in this cohort over the same time period, recognised 2-7yrs following NPC diagnosis.Presentation of IBD consisted of loose bowel motions, significant fistulating disease and large peri-anal skin tags. Four patients were receiving miglustat prior to diagnosis of IBD. Three patients were categorised as CD, and two as Very Early Onset (VEO-IBD) following endoscopic and histological assessment. All patients were diagnosed with severe fistulating disease. 4/5 patients had significantly large anal skin tags and 3/5 patients demonstrated labial / vulval disease. 4/5 patients were initiated on anti-aTNF therapy, but all patients required change of class / biologic. Three patients required colectomy. Two patients died at ages 2 and 17y.This cohort of patients represent a specific phenotype of IBD at presentation: significant anal skin tag, severe rectosigmoid disease with fistulating disease and high number with vulval involvement. All patients were female, which may significant. The clinical course is severe and challenging, demonstrated by severe disease at presentation, biologic class switch and a high number of colectomy. In addition, the neurological decline in patients with NPC can add to difficult interpretation of clinical progression. The GI side-effects of miglustat can be confused with presentation of IBD.Due to the rarity of NPC and the even lower incidence of IBD, the number of affected patients is small. However, when both conditions occur together, the disease presentation and progression tend to be particularly severe. This suggests that NPC may contribute to a distinct pathophysiological mechanism involving autophagy dysregulation and mucosal immune dysfunction.As active inflammation can accelerate neurodegeneration in NPC, we recommend routine screening for IBD in NPC patients with GI signs or symptoms. Multidisciplinary management involving gastroenterologists, neurologists, and geneticists is crucial to optimise care. Further research is needed to clarify the mechanistic links between NPC, autophagy impairment, and intestinal inflammation, which may reveal novel therapeutic targets for these complex cases.References Schwerd T, et al. Impaired antibacterial autophagy links granulomatous intestinal inflammation in Niemann–Pick disease type C1 and XIAP deficiency with NOD2 variants in Crohn’s disease. Gut. 2017;66:1060–1073.Williams I, Pandey S, Haller W, et al. Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease type C. Wellcome Open Res. 2022;7:11.",
  "authors": [
    {
      "affiliations": [
        "Department of Paediatric Gastroenterology, Sheffield Children’s Hospital"
      ],
      "name": "Sarah Bruce"
    },
    {
      "affiliations": [
        "Willink Metabolic Unit, Saint Mary’s Hospital, Manchester, UK"
      ],
      "name": "Aimee Donald"
    },
    {
      "affiliations": [
        "Willink Metabolic Unit, Saint Mary’s Hospital, Manchester, UK"
      ],
      "name": "Chern Tan"
    },
    {
      "affiliations": [
        "Department of Paediatric Gastroenterology, Great North Children’s Hospital, Newcastle"
      ],
      "name": "Anirban Mukhopadhyay"
    },
    {
      "affiliations": [
        "Department of Paediatric Gastroenterology, Royal Manchester Children’s Hospital"
      ],
      "name": "Sian Copley"
    },
    {
      "affiliations": [
        "Department of Paediatric Gastroenterology, Sheffield Children’s Hospital"
      ],
      "name": "Dominique Schluckebier"
    },
    {
      "affiliations": [
        "Department of Paediatric Gastroenterology, Sheffield Children’s Hospital"
      ],
      "name": "Akshay Kapoor"
    },
    {
      "affiliations": [
        "Willink Metabolic Unit, Saint Mary’s Hospital, Manchester, UK"
      ],
      "name": "Maria De Castro Lopez"
    },
    {
      "affiliations": [
        "Willink Metabolic Unit, Saint Mary’s Hospital, Manchester, UK"
      ],
      "name": "Simon Jones"
    }
  ],
  "title": "OC106 Niemann pick type C associated inflammatory bowel disease: a paediatric case series from a single centre",
  "uid": "6af98220-9d92-5a74-8f78-99dc550176a9"
}