Short and Long-Term Outcomes in Hirschsprung Disease: Are the Syndrome-Associated Patients Really Doing Worse?

INTRODUCTION: Given the lack of data to help caregivers in the follow-up of Hirschsprung disease (HD), this study aimed to compare the functional outcomes of isolated Hirschsprung disease (I-HD) to syndrome-associated Hirschsprung disease (SA-HD) at 1, 3, 5, and 10 years. METHODS: A retrospective chart review of patients diagnosed with HD between January 1990 and May 2021 at our pediatric center was performed to collect data on patient characteristics, investigations, and treatments. Ninety-five patients were identified, of whom 76 were included in the study. SA-HD is defined as a syndrome known to be associated with HD or cognitive impairment. RESULTS: Patient characteristics were comparable between groups ( P > 0.05). There were 52 patients with I-HD and 24 with SA-HD. The patients median age was 9 days at diagnosis and 1.5 month at surgery. SA-HD patients became bowel continent at a significantly older age (mean age 8.43 vs 4.94 years, P = 0.0471) and received more bowel continence medications. At 5 years, SA-HD patients requiring ≥2 medications for bowel continence represented 54.5% versus 11.1% of I-HD patients ( P = 0.009). Lastly, SA-HD patients had urinary incontinence at a significantly older age ( P = 0.0136, 5 years). CONCLUSION: Clinicians should be aware that SA-HD patients are more prone to bladder dysfunction and became bowel continent at an older age than I-HD patients. They need more and prolonged bowel management medications, and other important complications need to be addressed in patient care. These results should prompt a longer follow-up period for these patients, especially in SA-HD.

Early diagnosis and successful long-term management of a rare, severe lysosomal acid lipase deficiency/Wolman disease patient: Infancy to age five.

Background: This report describes a unique case of long-term survival of a young girl who was diagnosed with severe, rapidly progressive lysosomal acid lipase deficiency (LAL-D; historically "Wolman disease") at three months of age and began receiving therapeutic interventions at four months of age. This disease involves rapidly progressive multisystemic impairments and limited survival (6-12 months) without treatment. Methods: Case report taking into account clinical aspects and patient management including a semi-structured interview with the main family caregiver. Results: Presentation at two months of age: severe malnutrition and chronic diarrhea; hypoalbuminemia; low iron, vitamin A, and vitamin D levels; high triglyceride levels; profound anemia; thrombocytopenia; adrenal calcifications; and mild hepatosplenomegaly. Enzyme replacement therapy (ERT) with sebelipase alfa, parenteral nutrition, and a low-fat diet began at age four months. The patient has received sebelipase alfa for >5 years with good tolerability and is thriving, with a body mass index of 16.35 kg/m2 (80th percentile) despite a stature delay (height <3rd percentile), and mild developmental delay. Optimal medical management requires that family caregivers and health professionals have the knowledge and skills to provide appropriate care and supports multidisciplinary teams through transfer of knowledge to all stakeholders. Effective coordination of services and activities related to child health and development, including navigation of administrative and financial barriers, is also imperative. Conclusions: Formerly fatal in untreated infants, severe LAL-D, when diagnosed early, can be promptly and effectively treated by combining sebelipase alfa ERT, modified diet, involvement of family caregivers, and multidisciplinary team collaboration.

Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm.

The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-ß signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm.

Endoscopic assessment of children with esophageal atresia: Lack of relationship of esophagitis and esophageal metaplasia to symptomatology.

BACKGROUND: Late complications of esophageal atresia (EA), particularly esophagitis and Barrett's esophagus, are increasingly being recognized. With the exception of patients with dysphagia associated with esophageal stricture, it is unknown whether patient symptomatology can predict endoscopic findings. METHODS: Data regarding the digestive symptoms of patients who were referred to the EA multidisciplinary clinic from October 2005 to October 2008, and underwent upper gastrointestinal endoscopic evaluation, were systematically collected. Macroscopic and histological findings were analyzed. Endoscopy was considered normal if no esophagitis, intestinal metaplasia or gastric metaplasia (GM) was discerned. RESULTS: Sixty-three patients underwent endoscopy. Eighteen had dysphagia related to an esophageal stricture needing dilation and were subsequently excluded from the analysis. Forty-five patients (26 girls) with a median age of 7.3 years (range 0.4 to 17.9 years) were evaluated. Twenty-six patients (58%) were normal at endoscopy, 14 patients (31%) had esophagitis and 16 patients (36%) had GM. No intestinal metaplasia or adenocarcinoma was detected. Six patients with abnormal endoscopy results were asymptomatic. No correlation between digestive symptoms and endoscopy results was found. CONCLUSION: The present cross-sectional study showed that symptomatology was not predictive of abnormal endoscopy in EA patients. Esophagitis or GM may be discovered, even in the absence of symptoms, suggesting that physicians cannot rely solely on symptomatology to accurately evaluate the extent of these esophageal complications in this population.

Type A esophageal atresia: a critical review of management strategies at a single center.

PURPOSE: The purpose of was to study the short- and long-term outcomes in the management of isolated esophageal atresia with different operative strategies. METHODS: All patients undergoing type A atresia repair over a 15-year period were included. Demographic data, birth weight, gestational age, incidence of associated anomalies, management, and long-term outcomes were studied. RESULTS: Fifteen patients with type A atresia (9 male) were treated in the study period. The mean gestational age was 35.5 weeks (range, 27-39 weeks), and the mean birth weight was 2179 g (range, 670-3520 g). Eight babies had associated anomalies. Thirteen patients underwent gastrostomy as the initial procedure, and 2 underwent the Foker procedure. In the delayed management group, 9 patients underwent primary anastomosis, with 2 patients needing proximal pouch myotomy. Two patients underwent a Collis gastroplasty. Two patients underwent a cervical esophagostomy and a gastric tube replacement at 4 months and 1 year, respectively. Eight patients (60%) in this group had anastomotic leaks. All patients are currently on prokinetics and proton pump inhibitors. Seven required antireflux surgery. The median length of hospital admission was 4 months (range, 3-19 months). The native esophagus was preserved in 13 (85%) of 15 babies. All patients are alive, and 14 of 15 are capable of feeding orally. CONCLUSIONS: Type A esophageal atresia continues to be associated with significant morbidity despite advances in surgical technique and intensive care.

Risk factors for short- and long-term morbidity in children with esophageal atresia.

OBJECTIVE: To describe short- (first year of age) and long-term (after 1 year of age) outcome in patients with esophageal atresia and identify early predictive factors of morbidity in the first month of life. STUDY DESIGN: Charts of children with esophageal atresia born January 1990 to May 2005 were reviewed. A complicated evolution was defined as the occurrence of at least 1 complication: severe gastroesophageal reflux, esophageal stricture requiring dilatations, recurrent fistula needing surgery, need for gavage feeding for >or=3 months, severe tracheomalacia, chronic respiratory disease, and death. RESULTS: A total of 134 patients were included. Forty-nine percent of patients had a complicated evolution before 1 year of age, and 54% had a complicated evolution after 1 year. With bivariate analysis, predictive variables of a complicated evolution were demonstrated, including twin birth, preoperative tracheal intubation, birth weight <2500 g, long gap atresia, anastomotic leak, postoperative tracheal intubation >or=5 days, and inability to be fed orally by the end of the first month. After 1 year of age, the complicated evolution was only associated with long gap atresia and inability to be fed orally in the first month. A hospital stay >or=30 days was associated with a risk of a complicated evolution at 1 year and after 1 year of age (odds ratio, 9.3 [95% CI, 4.1-20.8] and 3.5 [95% CI, 1.6-7.6], respectively). CONCLUSION: Early factors are predictive of morbidity in children with esophageal atresia.

Is visceral hypersensitivity correlated with symptom severity in children with functional gastrointestinal disorders?

BACKGROUND: Abdominal pain related to irritable bowel syndrome (IBS) and functional abdominal pain (FAP) is frequent in children and can be of variable severity. Both IBS and FAP are associated with rectal hypersensitivity. We hypothesized that in children with IBS and FAP, the rectal sensory threshold for pain (RSTP) is associated with symptom severity. PATIENTS AND METHODS: A total of 47 patients (34 girls; median age, 14.2 years) with IBS (n = 29) and FAP (n = 18), according to the Rome II criteria, underwent a rectal barostat examination to determine their RSTP. Gastrointestinal symptom severity was assessed by validated questionnaires. During the rectal barostat exam, symptoms were documented using a visual analog scale and by measuring the area coloured on a human body diagram corresponding to painful sensations. RESULTS: The median RSTP was 16 mmHg and was similar in IBS and FAP patients. Eighty-three percent of the patients had rectal hypersensitivity (RSTP < or = 30.8 mmHg, the 5th percentile of control children studied in our laboratory). Fifty-one percent and 36%, respectively, reported missing school and social activities at least once per week. Increased frequency of pain, missed days of school, missed social activities, and pain during the barostat examination were not associated with lower RSTP values in either the whole group or in the subset of children with rectal hypersensitivity. CONCLUSIONS: Rectal hypersensitivity is not proportional to the severity of symptoms in children with IBS and FAP, indicating that symptom severity is influenced by other factors in addition to visceral hypersensitivity.