Alternative titles; symbols
SNOMEDCT: 722392003; ORPHA: 83620; DO: 0060779;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 10q22.1 | Diarrhea 4, malabsorptive, congenital | 610370 | Autosomal recessive | 3 | NEUROG3 | 604882 |
A number sign (#) is used with this entry because this form of congenital malabsorptive diarrhea, referred to here as DIAR4, is caused by mutation in the gene encoding neurogenin-3 (NEUROG3; 604882) on chromosome 10q22.
For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
Wang et al. (2006) reported 3 unrelated boys who presented with chronic unremitting malabsorptive diarrhea in the first weeks of life. Accompanying features included vomiting, dehydration, and severe hyperchloremic metabolic acidosis after the ingestion of standard cows-milk-based formula. The diarrhea ceased during periods of fasting, but returned with glucose- or amino acid-based oral solutions. All studies were negative for allergic, immunologic, infectious, and metabolic causes of diarrhea; pancreatic exocrine function was also normal. The children were discharged on parenteral nutrition and limited enteral feeding. One child died of sepsis at about 3 years of age; the other 2 continued to have large-volume loose stools daily and low weight. Both children developed type I diabetes (IDDM; 222100) at age 8 years. Small bowel biopsies showed normal villus structure and profound dysgenesis of the enteroendocrine cells. Only a few intestinal enteroendocrine cells stained positive for chromogranin A (CHGA; 118910); normal numbers of Paneth, goblet, and absorptive cells were observed. Wang et al. (2006) referred to the disorder as 'enteric anendocrinosis.'
In 3 unrelated boys with congenital malabsorptive diarrhea, Wang et al. (2006) identified 2 different homozygous mutations in the NEUROG3 gene (604882.0001; 604882.0002).
Wang, J., Cortina, G., Wu, S. V., Tran, R., Cho, J.-H., Tsai, M.-J., Bailey, T. J., Jamrich, M., Ament, M. E., Treem, W. R., Hill, I. D., Vargas, J. H., Gershman, G., Farmer, D. G., Reyen, L., Martin, M. G. Mutant neurogenin-3 in congenital malabsorptive diarrhea. New Eng. J. Med. 355: 270-280, 2006. [PubMed: 16855267] [Full Text: https://doi.org/10.1056/NEJMoa054288]