Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease

Description

To identify demographic, clinical, genetic, immunologic and/or microbial (i.e., fecal stream characterization) risk factors that influence the likelihood of development of the HAEC phenotype in children who carry the diagnosis of HD. The newly formed HAEC Collaborative Research Group (HCRG) will utilize the 4 participating centers in the current consortia and recruit additional centers to enroll children diagnosed with Hirschsprung disease. 1a: To recruit 200 patients with Hirschsprung disease without HAEC. 1b: To recruit 200 patients with Hirschsprung disease and HAEC using standardized diagnostic criteria by collaborating with participating members of the HAEC Collaborative Research Group\[1\]. 1c: To collect clinical and demographic information from well-characterized HD patients both with and without HAEC. 1d: To collect samples blood for DNA for genome wide association study (GWAS) by high throughput SNP technology and mutational analysis of known HSCR genes. 1e: To collect serum samples at the time of recruitment in a subset cohort (n=50 HD only, n=50 HD + HAEC) for serological immune markers known for inflammatory bowel disease (IBD) including ANCA, ASCA, OMPC, I2, and CBir1 and any newly identified markers. 1f: To collect and store fresh fecal specimens for future evaluation by molecular methodologies to determine relative proportions of enteric microflora in a subset cohort (n=50 HD only, n=50 HD + HAEC) of children (\<18 years). 1g: To establish a Centralized Data Coordinating Center for data collection, data quality and detailed data analyses (CSMC) and tissue bank (CSMC) to facilitate specimen analysis for this study. The HAEC risk factor identification will be completed by multivariate logistic regression analysis. Genetic association will be studied for each SNP in the GWAS together with all other potential risk factors. Further analysis will be carried out to evaluate multiple SNPs/genes simultaneously.

Conditions

Hirschsprung Disease, Enterocolitis

Study Overview

Study Details

Study overview

To identify demographic, clinical, genetic, immunologic and/or microbial (i.e., fecal stream characterization) risk factors that influence the likelihood of development of the HAEC phenotype in children who carry the diagnosis of HD. The newly formed HAEC Collaborative Research Group (HCRG) will utilize the 4 participating centers in the current consortia and recruit additional centers to enroll children diagnosed with Hirschsprung disease. 1a: To recruit 200 patients with Hirschsprung disease without HAEC. 1b: To recruit 200 patients with Hirschsprung disease and HAEC using standardized diagnostic criteria by collaborating with participating members of the HAEC Collaborative Research Group\[1\]. 1c: To collect clinical and demographic information from well-characterized HD patients both with and without HAEC. 1d: To collect samples blood for DNA for genome wide association study (GWAS) by high throughput SNP technology and mutational analysis of known HSCR genes. 1e: To collect serum samples at the time of recruitment in a subset cohort (n=50 HD only, n=50 HD + HAEC) for serological immune markers known for inflammatory bowel disease (IBD) including ANCA, ASCA, OMPC, I2, and CBir1 and any newly identified markers. 1f: To collect and store fresh fecal specimens for future evaluation by molecular methodologies to determine relative proportions of enteric microflora in a subset cohort (n=50 HD only, n=50 HD + HAEC) of children (\<18 years). 1g: To establish a Centralized Data Coordinating Center for data collection, data quality and detailed data analyses (CSMC) and tissue bank (CSMC) to facilitate specimen analysis for this study. The HAEC risk factor identification will be completed by multivariate logistic regression analysis. Genetic association will be studied for each SNP in the GWAS together with all other potential risk factors. Further analysis will be carried out to evaluate multiple SNPs/genes simultaneously.

Identification of Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease

Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease

Condition
Hirschsprung Disease
Intervention / Treatment

-

Contacts and Locations

Los Angeles

Cedars-Sinai Medical Center 8723 Alden Drive, Suite 240, Los Angeles, California, United States, 90048

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * 1. Males and females of all ages with a confirmed diagnosis of HD based on standardized histological criteria. Only Males and females ages 0 to 17 with a confirmed diagnosis of HD based on standardized histological criteria will be enrolled at CSMC.
  • * 2. Able to provide written informed assent if between the ages of 7 and 17. If age 6 and under, able to participate with parental permission.
  • * 3. Have consented to have specimens tested for genetics, immune responses, stool microflora.
  • * 1)Documented histopathology showing absence of ganglion cells and is consistent with the diagnosis of HD.
  • * 1. Intestinal neuronal dysplasia
  • * 2. Pseudo-obstruction

Ages Eligible for Study

1 Day to 17 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Cedars-Sinai Medical Center,

Philip K Frykman, MD, PhD, MBA, PRINCIPAL_INVESTIGATOR, Associate Professor, Surgery and Biomedical Sciences Associate Director, Pediactic Surgery for Cedars-Sinai Medical Center

Study Record Dates

2025-12