Reversal of Intestinal Failure in Children With Tufting Enteropathy Supported With Parenteral Nutrition at Home

Ashworth, I; Wilson, Andy; Aquilina, Susan; Parascandalo, Raymond; Mercieca, Victor; Gerada, Jurgen; MacDonald, Sarah; Simchowitz, Venetia; Hill, Susan

doi:10.1097/mpg.0000000000001894

Cited by 17 publications

(20 citation statements)

References 21 publications

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“…Our reports demonstrate the need to diagnose and treat PN-related complications to decrease the mortality of this disorder. We confirm previous observations that patients with TE can survive the first year(s) of life with breastfeeding or formula, despite the severe diarrhea, at the cost of stunted growth [5,22].…”

Section: Discussionsupporting

confidence: 90%

Three Novel EPCAM Variants Causing Tufting Enteropathy in Three Families

et al. 2021

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Tufting enteropathy (TE) is caused by recessive EPCAM mutations, and is characterized by intractable diarrhea of congenital onset and disorganization of enterocytes. TE generally requires parenteral nutrition (PN) during childhood or intestinal bowel transplantation. We report three unrelated families with six children with TE. We highlight the high rate of disease-related mortality. We observe adequate weight gain with PN, but low to normal and stunted body length, supporting the recent notion that a short stature might be intrinsic to TE. The diagnosis of TE in the index patients from each family was delayed for months to years, even when clinical data, duodenal biopsies, or exome sequencing data were obtained early on. We identified three novel pathogenic EPCAM variants: a deletion of exon 1 that removes the ATG initiation codon, a missense variant c.326A > G (p.Gln109Arg), and nonsense mutation c.429G > A (p.Trp143*) in a compound heterozygous state with the Mediterranean splice site variant c.556-14A > G (Tyr186Phefs*6). Homozygosity for p.Gln109Arg was associated with absent EPCAM staining, and compound heterozygosity for p.Trp143*/Tyr186Phefs*6 was associated with reduced EPCAM staining in duodenal biopsies; such observations might contribute to a genotype–phenotype correlation in larger cohorts of TE patients. This study extends the clinical and molecular spectrum of TE.

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Section: Discussionsupporting

confidence: 90%

Three Novel EPCAM Variants Causing Tufting Enteropathy in Three Families

et al. 2021

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“…A longterm follow-up study of 13 tufting enteropathy patients showed a survival rate of more than 92% for those who relied on parenteral nutrition at home. 21 There was only one CGM case with SLC5A1 pathogenic variants in the Chinese population. 22 In this study, we examined the second case by panel sequencing.…”

Section: Patients With Watery Stoolmentioning

confidence: 98%

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

Huang

Zheng

Wang

et al. 2019

Genetics in Medicine

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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.

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“…Currently there is no special treatment for CTE patients. Samuel Aquiline et al reported that 13 patients with CTE were treated with long-term family parenteral nutrition [9]. Finally, 12 patients survived for 8 to 30 years under long-term parenteral nutrition therapy and the proportion of weaning off parenteral nutrition gradually increased with age.…”

Section: Discussionmentioning

confidence: 99%

A case of severe malnutrition infant with neonatal onset intractable diarrhea

Fang

Luo

et al. 2020

BMC Pediatr

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Background: Congenital tufting enteropathy (CTE) is a rare disease that manifests as intractable diarrhea during the neonatal period which is associated with mutations of the epithelial cell adhesion molecule (EpCAM) gene. Case presentation: A male infant who presented with vomiting, diarrhea, abdominal distention, malnutrition and growth failure was admitted to our department when he was 2 months old. His parents were healthy and nonconsanguineous. Etiologic examinations of stool, inflammatory markers, blood gas and electrolytes levels, serum albumin level, serum immunoglobin levels were all normal. And there was no indication for metabolic diseases. Additionally, gastrointestinal contrast did not reveal abnormality of gastrointestinal. The patient was diagnosed with intestinal malabsorptive syndrome and severe malnutrition without definite cause. He was on supportive treatment and nutritional therapy for 13 months. However, he did not gain weight obviously. He was discharged at the age of 15 months and was fed with partial hydrolyzed formula and rice paste at home. Three months later he developed hypoglycemia and severe respiratory infection. Finally, he died due to sepsis and multiple organs failure. The next generation sequencing revealed one homozygous mutation of EpCAM gene and one complex heterozygous mutation of TTC7A gene. He was diagnosed CTE according to the genetic results and clinical manifestations. Conclusions: CTE is rarely reported in Asia. Patients present with congenital diarrhea, poor weight gain and growth failure are recommended to perform endoscopy examination with proper immunohistochemistry study as early as possible, and genetic testing is necessary when suspecting congenital diarrhea and enteropathy.

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Reversal of Intestinal Failure in Children With Tufting Enteropathy Supported With Parenteral Nutrition at Home

Abstract: IED cases should have >92% chance of long-term survival and >50% chance of enteral autonomy by/in early adult life and 75% by 25 years. Even if PN dependent s/he can gain employment. Patients with IED managed on PN at home by an IF rehabilitation service should avoid intestinal transplant.

Cited by 17 publications

References 21 publications

Three Novel EPCAM Variants Causing Tufting Enteropathy in Three Families

Three Novel EPCAM Variants Causing Tufting Enteropathy in Three Families

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

A case of severe malnutrition infant with neonatal onset intractable diarrhea

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