Severe congenital diarrhea secondary to tufting enteropathy. case report

ABSTRACT Introduction: Tufting enteropathy is a rare cause of congenital diarrhea in neonates. It is characterized by the abnormal distribution of epithelial adhesion molecules, which causes enterocytes to shed into the lumen, forming the characteristic tufts. Case summary: A 15-day-old female neonate was taken by her parents to the emergency department of a tertiary care hospital due to diarrheal stools she had been experiencing since birth. The patient presented with dehydration, abnormal weight loss, metabolic acidosis, and acute kidney failure. She received treatment with alizapride, loperamide, zinc sulfate, and probiotics, but after 75 days of treatment she was still symptomatic. An upper tract endoscopy and colonoscopy were performed, finding flattening of the villi and lymphoid cells in the lamina propria. However, the symptoms persisted, and she died at the age of ten months. A post-mortem exome sequencing reported tufting enteropathy. Conclusions. When congenital diarrhea is present, tufting enteropathy should be considered. An early molecular study would allow to evaluate the possibility of performing an intestinal transplant or modifying the treatment to meet the patient's palliative care needs.

RESUMEN Introducción. La enteropatía en penacho es una causa rara de diarrea congénita en neonatos; esta se caracteriza por una alteración de la adhesión epitelial que ocasiona desprendimiento de enterocitos hacia el lumen y, en consecuencia, forma los característicos penachos. Se describe el caso de una paciente con esta patología. Presentación del caso. Neonata de 15 días de vida, quien fue llevada por sus padres al servicio de urgencias de un hospital de tercer nivel debido a que desde su nacimiento tuvo deposiciones diarreicas y a causa de esto presentó deshidratación, pérdida de peso, acidosis metabólica e insuficiencia renal aguda. La paciente recibió manejo con alizaprida, loperamida, sulfato de zinc y probióticos, pero a los 75 días de tratamiento continuaba sintomática. Se le practicó una endoscopia de vías digestivas y una colonoscopia que mostraron aplanamiento de las vellosidades e infiltrado de células linfoides en la lámina propia. Los síntomas continuaron y la menor falleció a los 10 meses de nacida. El resultado del exoma post mortem reportó enteropatía en penacho. Conclusiones. Ante la presencia de diarrea congénita, se debe sospechar de una enteropatía en penacho y considerar el estudio molecular temprano, pues este permite evaluar la posibilidad de realizar un trasplante intestinal o modificar el tratamiento según las necesidades de cuidado paliativo del paciente.

Enteropatia com formação de tufos epiteliais e mutação do gene EpCAM: relato de caso / Tufting enteropathy with EpCAM mutation: case report

Tufting enteropathy (TE), also known as intestinal epithelial dysplasia (IED), is a rare congenital enteropathy related to an earlyonset of severe intractable diarrhea due to specific abnormalities of the intestinal epithelium and mutations of the EpCAM gene. TE is characterized by clinical and histological heterogeneity, such as with low or without mononuclear cell infiltration of the lamina propria, and abnormalities of basement membrane. TE can be associated with malformations, other epithelial diseases, or to abnormal enterocytes development and/or differentiation. The authors report a case of a Brazilian child with TE associated with c.556-14A>G mutation in the EpCAM gene (NM_002354.2)...

Enteropatia com formação de tufos epiteliais (ETE), também conhecida como displasia epitelial intestinal (DEI), é uma rara enteropatia congênita relacionada com um início precoce de diarreia intratável grave devido a anormalidades específicas do epitélio intestinal e mutações do gene EpCAM. ETE caracteriza-se por uma heterogeneidade clínica e histológica, como ausência ou leve infiltrado de células mononucleares na lâmina própria e anormalidades de membrana basal. Pode ser associada a malformações, outras doenças epiteliais ou anormalidades no desenvolvimento/na diferenciação dos enterócitos. Os autores relatam um caso de ETE, em uma criança brasileira, associada à mutação c.556-14A> g do gene EPCAM (NM_002354.2)...

Tufting Enteropathy with EpCAM Mutations in Two Siblings

Tufting enteropathy is a rare autosomal recessive disorder presenting with early-onset severe intractable diarrhea. The epithelial cell adhesion molecule gene (EpCAM) has recently been identified as the gene responsible for tufting enteropathy. Based on histology, a diagnosis of tufting enteropathy was made in two Korean siblings. They developed chronic diarrhea and failure to thrive. They had a broad nasal bridge and micrognathia. Duodenal and colonic biopsies showed villous atrophy, disorganization of surface enterocytes, and focal crowding resembling tufts. Protracted diarrhea continued and so cyclic parenteral nutrition was supplied. The sister had juvenile rheumatoid arthritis. Mutation analysis of EpCAM identified two compound heterozygous mutations in these siblings: 1) a donor splicing site mutation in intron 5 (c.491+1G>A) and 2) a novel nonsense mutation in exon 3 (c.316A>T, Lys106X). Analysis of EpCAM will be useful for genetic counseling and prenatal diagnosis of tufting enteropathy.