Clinical and genetic spectrum of children with congenital diarrhea and enteropathy in China

Genet Med. 2019 Oct;21(10):2224-2230. doi: 10.1038/s41436-019-0488-z. Epub 2019 Mar 21.


Purpose: Genetic sequencing for children with congenital diarrhea and enteropathy (CODE) has important implications for the diagnosis, prognosis, and implementation of precision medicine.

Methods: We performed exome sequencing or targeted panel sequencing on 137 children with CODE. Endoscopic, imaging, histological, and immunological assessments were also applied. Patients were divided into three subgroups: watery, fatty, and bloody diarrhea.

Results: The median age of onset among patients was 28.0 (interquartile range: 7.5-120.0) days. Genetic diagnosis was achieved in 88/137 (64.2%) of patients. The diagnostic rate was significantly higher in the neonatal group than in the group of patients who had disease onset within 2 years of age (p = 0.033). The diagnostic rates were 71.9% (46/64) for targeted gene panel sequencing and 57.5% (42/73) for exome sequencing (p = 0.081). We identified pathogenic variants in 17 genes. Based on genetic sequencing, 59.9% of patients were diagnosed with medically actionable disorders. Precision medicine was carried out by means of hematopoietic stem cell transplantation for patients with IL10RA, CYBB, or FOXP3 deficiency; pancreatic enzyme replacement for patients with SBDS or UBR1 deficiency; and a special diet for patients with SLC5A1 deficiency. The overall mortality rate was 14.6%.

Conclusion: Single-gene disorders are common among CODE patients. Genetic diagnosis can improve therapy by enabling precision medicine.

Keywords: congenital; diarrhea; enteropathy; genetics; monogenic.

MeSH terms

  • Child
  • Child, Preschool
  • China
  • Diarrhea / genetics*
  • Diarrhea, Infantile / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation
  • Phenotype
  • Whole Exome Sequencing / methods