A Novel Homozygote EpCAM Gene Mutation in Turkish Neonate with Tufting Enteropathy

Abstract

Congenital tufting enteropathy is characterized by intractable watery diarrhea, weight loss, malnutrition and growth retardation in newborn. It is a rare autosomal recessive disorder which is caused by mutations in the gene encoding human epithelial cell adhesion molecule (EpCAM). The diagnosis is based on a combination of clinical signs, histological findings and genetic tests that identify a mutation in the EPCAM gene. We report a Turkish neonate with congenital tufting enteropathy presenting to the emergency department with severe watery diarrhea and weight loss. He was diagnosed as having congenital tufting enteropathy based on his clinical signs and genetic analysis. He was fed by total parenteral nutrition and carbohydrate-poor formula. Despite fact that it is often difficult to find the etiology of conditions that cause congenital diarrhea, clinical suspicion and genetic analysis might be helpful in making the diagnosis of congenital tufting enteropathy.

Keywords

• congenital diarrhea
• tufting enteropathy
• epithelial cell adhesion molecule
• infant

Tufting Enteropatili Türk Yenidoğan'da Yeni Bir Homozigot EpCAM Gen Mutasyonu

Abstract

Konjenital tufting enteropati (KTE), yenidoğan döneminde dirençli sulu ishal, kilo kaybı, yetersiz beslenme ve büyüme geriliği ile karakterizedir. KTE, insan epitel hücre adezyon molekülünü (EpCAM) kodlayan gendeki mutasyonların neden olduğu nadir görülen otozomal resesif bir hastalıktır. Tanı klinik bulgular, histolojik bulgular ve EPCAM genindeki mutasyonu tanımlayan genetik testlerin birlikteliği ile koyulur. Acil servise şiddetli sulu ishal ve kilo kaybı şikayetleri ile başvuran ve konjenital tufting enteropati tanısı koyulan bir Türk yenidoğan olgusu sunulmuştur. Hastaya, klinik bulgularına ve genetik analiz sonucuna dayanılarak konjenital tufting enteropati tanısı koyuldu. Total parenteral beslenme ve karbonhidrattan fakir mama ile beslendi. Konjenital ishalin etiyolojisini saptamak genellikle zor olsa da, klinik şüphe ve genetik analiz, konjenital tufting enteropatinin teşhisinde faydalı olabilir.

Keywords

• konjenital diyare
• tufting enteropati
• epitel hücre adezyon molekülü
• infant

References

1. 1. Goulet O, Salomon J, Ruemmele F, et al. Intestinal epithelial dysplasia (tufting enteropathy). Orphanet J Rare Dis. 2007; 2: 20.
2. 2. Reifen RM, Cutz E, Griffiths AM, et al. Tufting enteropathy: a newly recognized clinicopathological entity associated with refractory diarrhea in infants. J Pediatr Gastroenterol Nutr 1994;18:379–385.
3. 3. Sivagnanam M, Mueller JL, Lee H, et al. Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology 2008;135:429–37. https://doi.org/10.1053/j.gastro.2008.05.036.
4. 4. Das B, Sivagnanam M. Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms. J. Clin. 2020;10(1):19. https://doi.org/10.3390/jcm10010019.
5. 5. Cai C, Chen Y, Chen X, et al. Tufting Enteropathy: A Review of Clinical and Histological Presentation, Etiology, Management, and Outcome. Gastroenterol Res Pract. (2020);2020:5608069. https://doi.org/10.1155/2020/5608069.
6. 6. Paramesh AS, Fishbein T, Tschernia A, et al. Isolated small bowel transplantation for tufting enteropathy. J Pediatr Gastroenterol Nutr 2003;36:138 –140.
7. 7. Ashworth I, Wilson A, Aquilina S, et al. Reversal of intestinal failure in children with tufting enteropathy supported with parenteral nutrition at home. J Pediatr Gastroenterol Nutr. 2018;66(6):967-971.
8. 8. Kahvecioğlu D, Yıldız D, Kılıç A, et al. A rare cause of congenital diarrhea in a Turkish newborn: tufting enteropathy. Turk J Pediatr. 2014;56(4):440-3.

9. 9. Haas K, Martin B, Martin M, et al. Intractable diarrhea in two brothers: late diagnosis of tufting enteropathy in adolescence. Dig Dis Sci. 2016;61:381–383.
10. 10. Tang W, Huang T, Xu, et al. Novel Mutations in EPCAM Cause Congenital Tufting Enteropathy. J Clin Gastroenterol. 2018;52(1):1-6.
11. 11. Pegas KL, Cambruzzi E, Ferrelli RS, et al. Tufting enteropathy with EpCAM mutation: Case report. J. Bras. Patol. Med. Lab. 2014;50 (3): 234-237. https://doi.org/10.5935/1676-2444.20140021.
12. 12. Bosaleh A, Contreras M, García de Dávila MT. Enteropatía en penacho: reporte de un caso, metodología de estudio de la biopsia y diagnósticos diferenciales [Tufting enteropathy: a case report, methodology, and differential diagnoses]. Acta Gastroenterol Latinoam. 2015;45(1):65-9.
13. 13. Güvenoğlu M, Şimşek-Kiper PÖ, Koşukcu C, et al. Homozygous Missense Epithelial Cell Adhesion Molecule Variant in a Patient with Congenital Tufting Enteropathy and Literature Review. Pediatr Gastroenterol Hepatol Nutr. 2022;25(6):441-452. https://doi.org/10.5223/pghn.2022.25.6.441.
14. 14. Salomon J, Goulet O, Canioni D, et al. Genetic characterisation of congenital tufting enteropathy: epcam associated phenotype and involvement of SPINT2 in the syndromic form. Human Genetics. 2014;133:299-310.
15. 15. Roche O, Putterman M, Salomon J, et al. Superficial punctate keratitis and conjunctival erosions associated with congenital tufting enteropathy. Am J Ophthalmol 2010;150:116-211. https://doi.org/10.1016/j.ajo.2010.01.034.
16. 16. Pathak SJ, Mueller JL, Okamoto K, et al. EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome. Hum Mutat. 2019;40(2):142-161. https://doi.org/10.1002/humu.23688.
17. 17. Landrum JM, Chitipiralla S, Brown GR, et al. ClinVar: improvements to accessing data. Nucleic Acids Research, 2020;48(1):835–844. https://doi.org/10.1093/nar/gkz972.