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.