Severe gastrointestinal motility disorders with small bowel involvement continue to pose a major clinical challenge to clinicians, particularly because of the limitations of diagnostic tests and the lack of efficacious treatment options. In this article, we review current understanding and the utility of diagnostic modalities and therapeutic approaches, and describe how their limitations may potentially exacerbate prolonged suffering with debilitating symptoms, diagnostic delays, the risk of iatrogenic harm and increased healthcare utilisation in this group of patients. Moreover, observations from intestinal failure units worldwide suggest that this problem could be set to increase in the future, with reported trends of increasing numbers of patients presenting with nutritional consequences. Unfortunately, until recently, there has been a lack of consensus recommendations and guidance to support clinicians with their management approach. The aim of this narrative review is to summarise recent developments in this field following publication of an international census of experts, and subsequent clinical guidelines, which have emphasized the importance of holistic, multidisciplinary care. This is particularly important in achieving good clinical outcomes and ensuring the appropriate use of artificial nutritional support, in order to prevent iatrogenic harm. We discuss how these recent developments may impact clinical practice by supporting the development of specialised clinical services to deliver optimal care, and highlight areas where further research is needed.

Chronic intestinal pseudoobstruction (CIPO) is a severe form of intestinal dysmotility, and patients often undergo iterative abdominal surgeries and require parenteral nutrition. Several genes are known to be responsible for this pathology, including ACTG2 (autosomal dominant) and MYH11 (autosomal recessive). We report the first case of unexpected trio medical exome sequencing diagnosis of mucopolysaccharidosis type I (MPS-I) in a patient with an early CIPO. There was no clinical suspicion of MPS-I at the time of the prescription. It allowed biochemical confirmation of MPS-I, expert clinical evaluation and early treatment. Enzyme replacement therapy (ERT) with laronidase was started at 9 months old, and hematopoietic stem cell transplantation was carried out at 10 months and a half. The patient also had a 1.7 mb heterozygous deletion in chromosomal region 16p13.11p12.3, comprising several genes, including MYH11, paternally inherited. Her father has no symptoms of CIPO or other digestive symptoms. One previous association of CIPO and MPS-I was reported in 1986. Moreover, the number of incidental findings of inherited metabolic disorders with therapeutic impact will inevitably increase as pangenomic analyses become cheaper and easily available.

OBJECTIVE: Small bowel dysmotility is a broad heterogeneous term that encompasses a wide range of gastrointestinal disorders resulting from abnormal gut motility. Chronic intestinal pseudo-obstruction (CIPO) is a severe, rare, and complex small bowel motility disorder at the extreme end of this spectrum. It is characterized by failure of the intestinal tract to propel contents, which results in signs and symptoms of bowel obstruction albeit in the absence of any obstructive lesion(s). In this article, we discuss up-to-date diagnostic techniques, management options, and histopathological findings in CIPO.
RESULTS: We will emphasize the latest diagnostic methodologies and therapeutic options as well as enteric histopathologic abnormalities in patients with CIPO. CIPO continues to be a clinical challenge. Several novel pharmacological agents hold promise including gastrointestinal hormone agonists and prokinetics. Furthermore, histopathologic findings may help guide therapy and provide further prognostic significance. At present, nutritional support, symptom management, and avoidance of long-term complications are the mainstay of treatment in CIPO.

Primary visceral myopathy caused by a pathogenic mutation in the gene encoding the enteric smooth muscle actin gamma 2 ( ACTG2) affects gastrointestinal and genitourinary tracts and often presents as chronic intestinal pseudoobstruction. We present a case of pediatric onset chronic intestinal pseudoobstruction associated with a novel missense ACTG2 mutation c.439G>T/p.G147C. In addition to the known disease manifestations of feeding intolerance and intestinal malrotation, our patient had a late-onset hypertrophic pyloric stenosis and a late-onset choledochal cyst, the former of which has not previously been described in patients with ACTG2-associated visceral myopathy.