Genetic and acquired sucrase-isomaltase deficiency: A clinical review.

Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene. Congenital sucrase-isomaltase deficiency is historically considered to be a rare condition affecting infants with chronic diarrhea as exposure to dietary sucrose begins. Growing evidence suggests that individuals with SI variants may present later in life, with symptoms overlapping with those of irritable bowel syndrome. The presence of SI genetic variants may, either alone or in combination, affect enzyme activity and lead to symptoms of different severity. As such, a more appropriate term for this inherited condition is GSID, with a recognition of a spectrum of severity and onset of presentation. Currently, disaccharidase assay on duodenal mucosal tissue homogenates is the gold standard in diagnosing SI deficiency. A deficiency in the SI enzyme can be present at birth (genetic) or acquired later, often in association with damage to the enteric brush-border membrane. Other noninvasive diagnostic alternatives such as sucrose breath tests may be useful but require further validation. Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms. As this approach may be challenging, additional treatment with commercially available sacrosidase is available. However, some patients may require continued starch restriction. Further research is needed to clarify the true prevalence of SI deficiency, the pathobiology of single SI heterozygous mutations, and to define optimal diagnostic and treatment algorithms in the pediatric population.

Utility of colonic manometry in children with Hirschsprung disease.

OBJECTIVES: Abnormal motility of the residual colon has been reported in post-pull-through Hirschsprung disease (PT-HSCR) patients with persistent defecation problems. We reviewed the role of colonic manometry (CM) in the management of defecation disorders in these patients. METHODS: We retrospectively reviewed the medical record of PT-HSCR children who underwent CM for persistent symptoms of abnormal defecation. We reviewed their clinical course and its relation to CM findings. RESULTS: Thirty PT-HSCR patients underwent CM, of which five were diagnosed with transition zone pull-through and were excluded. Of the remaining 25 patients, 16 had colonic dysmotility, 8 had normal CM, and one had colonic hypermotility. In patients with dysmotility, five responded to ongoing medical management, three required surgical intervention (ileostomy), three remained symptomatic with medical management but not yet received surgical intervention, and five were lost to follow-up. In patients with normal CM, four responded to ongoing medical therapy, two required additional surgery (antegrade enema procedure), and two were lost to follow-up. The patient with hypermotility improved with adding loperamide. CONCLUSIONS: Colonic dysmotility can occur in PT-HSCR patients with persistent defecation problems. CM was helpful in delineating the degree of colonic neuromuscular dysfunction. CM results were used in conjunction with other clinical data to determine optimal management. Our findings support that medical management should first be optimized before consideration of colonic manometry and surgical interventions.

Hirschsprung disease and other gastrointestinal motility disorders in patients with CCHS.

Congenital central hypoventilation syndrome (CCHS) is an autonomic nervous system dysfunction due to PHOX2B gene mutation. Little is known about gastrointestinal motility disorders in CCHS patients. This study aims to describe the spectrum of gastrointestinal motility disorders in CCHS and provide PHOX2B genotype-phenotype correlation with Hirschsprung Disease (HD). We reviewed the records of 72 CCHS patients seen at Children's Hospital Los Angeles from 1999 to 2019. Data collected included demographics, PHOX2B genotype, ventilator dependence, medical and surgical history, and gastrointestinal motility studies. Of the 72 patients, 31% had HD, 50% females, and 60% had 20/27 PARM. Rectosigmoid HD formed 73% of the cases whereas long segment (up to splenic flexure involvement) forms represented 23%. Four patients had total colonic aganglionosis, including one patient with 20/25 PARM genotype. One HD patient was identified with colonic myopathy in the residual segment. One patient was found to have achalasia type 1.Conclusion: Nearly one third of our CCHS patients had HD. Although most had 20/27 PARM, 2 patients had 20/25 PARM. Thus, CCHS patients with constipation are at risk for HD regardless of genotype. Colonic myopathy may coexist in treated HD with refractory constipation. Achalasia may occur in patients with CCHS. What is Known: • Patients with CCHS have motility disorders and present with esophageal dysmotility and constipation as a manifestation of their autonomic nervous system dysfunction. • About 20% of patients with CCHS have Hirschsprung disease and previously described to be associated with NPARM and 20/27 PARM genotype. What is New: • Thirty-one percent of CCHS patients in our series have Hirschsprung disease (HD). • HD, including the more severe total colonic aganglionosis was found in a patient with 20/25 PARM genotype suggesting that CCHS patients with constipation should be screened for HD regardless of genotype.

Proceedings of the 2018 Advances In Motility and In NeuroGastroenterology: AIMING for the Future Single Topic Symposium.

OBJECTIVES: Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology - AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies. METHODS: The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought-provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment-based approach. CONCLUSIONS: The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.

Comparison of Diagnostic Accuracy and Concordance of Video Capsule Endoscopy and Double Balloon Enteroscopy in Children.

OBJECTIVES: To compare the diagnostic yield, sensitivity, and specificity of video capsule endoscopy (VCE) with double balloon enteroscopy (DBE), including comparison with histological findings as well as degree of concordance of the studies. METHODS: Retrospective review of pediatric patients who had DBE following VCE at a single center from 2006 to 2013. VCEs were interpreted by 1 of 4 pediatric gastroenterologists and DBEs were performed by a single endoscopist. RESULTS: Thirty-six patients ranging from 5 to 20 years had DBE following VCE. There were positive findings in 32 (88.8%) of VCE and 21 (58.3%) of DBE. Significant histological findings were identified in 16 patients (44.4%). When comparing VCE with DBE findings, VCE had a sensitivity of 95% and specificity of 20%. Overall concordance between VCE and DBE findings was weak with calculated kappa index of 0.1702; however, this varied widely by indication. VCE had sensitivity 100% and specificity 20% for detecting histologically significant lesions. DBE had sensitivity of 87% and specificity of 65%. CONCLUSIONS: This is the first pediatric study to evaluate diagnostic accuracy and concordance of VCE and DBE and to compare both to histological findings. Our study supports the high diagnostic utility of both the studies. VCE is highly sensitive with an excellent negative predictive value both for DBE findings and for histological findings; however, the utility of VCE is limited by low specificity. Sensitivity and specificity of DBE for detecting histologically significant findings were good. Overall agreement between VCE and DBE is low but varies by indication for the study. These results support the use of VCE and DBE as complementary studies.

Changing definitions of successful outcomes in pediatric liver transplantation.

PURPOSE OF REVIEW: This review highlights the fact that in the current era, the focus of success in pediatric transplantation has moved from short-term to long-term patient and graft survival as well as achieving 'normality' after transplantation. RECENT FINDINGS: Advances in surgical techniques, organ allocation, intensive care management, laboratory tests, interventional and diagnostic radiology, immunosuppressive, and antiviral drugs have allowed a larger number of pediatric liver transplant recipients to progress into adulthood. To achieve 'normality' several medical and psychosocial factors have become the target of intervention. Attaining optimal linear growth and puberty after transplant is important as is minimizing adverse events associated with immunosuppression. Special considerations are important in the adolescent transplant recipient, particularly adherence to medical recommendations. Liver transplant recipients have been reported to have below average intelligence quotient at school entry and significantly lower health-related quality of life than healthy controls and appropriate interventions need to be put in place early. Successful long-term outcomes in transplantation are contingent on successful transition from pediatric to adult healthcare services. Achieving operational tolerance remains a goal. SUMMARY: In conclusion, this review outlines the myriad issues around pediatric transplantation that can be addressed so that the transplant recipient may experience a 'normal' quality of life.