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Congenital malabsorptive diarrhea 4(DIAR4)

MedGen UID:
372151
•Concept ID:
C1835888
•
Disease or Syndrome
Synonym: ENTERIC ANENDOCRINOSIS
SNOMED CT: Congenital malabsorptive diarrhea due to paucity of enteroendocrine cells (722392003); Enteric anendocrinosis (722392003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): NEUROG3 (10q22.1)
 
Monarch Initiative: MONDO:0012479
OMIM®: 610370
Orphanet: ORPHA83620

Definition

An exceedingly rare genetic gastroenterological disease characterized by severe malabsorption diarrhea and a lack of intestinal enteroendocrine cells. Within the first weeks of life, patients present with vomiting, dehydration and severe diarrhea unresponsive to various nutrients and formulas and require home parenteral nutrition. The syndrome is also associated with type 1 diabetes during childhood. This phenotype is caused by loss-of-function mutations in the NEUROG3 gene, coding for neurogenin 3, a protein implicated in endocrine enteric and pancreatic cell development. [from SNOMEDCT_US]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
•Concept ID:
C2315100
•
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
See: Feature record | Search on this feature
Diarrhea
MedGen UID:
8360
•Concept ID:
C0011991
•
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
See: Feature record | Search on this feature
Vomiting
MedGen UID:
12124
•Concept ID:
C0042963
•
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
See: Feature record | Search on this feature
Dehydration
MedGen UID:
8273
•Concept ID:
C0011175
•
Disease or Syndrome
A condition resulting from the excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.
See: Feature record | Search on this feature
Hyperchloremic metabolic acidosis
MedGen UID:
369924
•Concept ID:
C1969073
•
Disease or Syndrome
A form of metabolic acidosis with increased serum chloride levels.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital malabsorptive diarrhea 4
Follow this link to review classifications for Congenital malabsorptive diarrhea 4 in Orphanet.

Professional guidelines

PubMed

Value of breath hydrogen analysis in management of diarrheal illness in childhood: comparison with duodenal biopsy.
Davidson GP, Robb TA
J Pediatr Gastroenterol Nutr 1985 Jun;4(3):381-7. doi: 10.1097/00005176-198506000-00010. PMID: 4020571

Recent clinical studies

Etiology

Congenital Rare Diseases Causing Persistent Diarrhea in the Newborn: A Single Center Experience.
Hoşnut FÖ, Sahin GE, Ozyazıcı A, Olgac A, Aksu AU
Z Geburtshilfe Neonatol 2022 Oct;226(5):311-318. Epub 2022 May 16 doi: 10.1055/a-1774-5005. PMID: 35576965
Genetic Enteropathies Linked to Epithelial Structural Abnormalities and Enteroendocrine Deficiency: A Systematic Review.
Caralli M, Roman C, Coste ME, Roquelaure B, Buffat C, Bourgeois P, Badens C, Fabre A
J Pediatr Gastroenterol Nutr 2021 Jun 1;72(6):826-832. doi: 10.1097/MPG.0000000000003049. PMID: 33976085
Sucrase-Isomaltase Deficiency as a Potential Masquerader in Irritable Bowel Syndrome.
Kim SB, Calmet FH, Garrido J, Garcia-Buitrago MT, Moshiree B
Dig Dis Sci 2020 Feb;65(2):534-540. Epub 2019 Sep 6 doi: 10.1007/s10620-019-05780-7. PMID: 31493040
Congenital intestinal diarrhoeal diseases: A diagnostic and therapeutic challenge.
Posovszky C
Best Pract Res Clin Gastroenterol 2016 Apr;30(2):187-211. Epub 2016 Mar 11 doi: 10.1016/j.bpg.2016.03.004. PMID: 27086885
Congenital diarrheal disorders: an updated diagnostic approach.
Terrin G, Tomaiuolo R, Passariello A, Elce A, Amato F, Di Costanzo M, Castaldo G, Canani RB
Int J Mol Sci 2012;13(4):4168-4185. Epub 2012 Mar 29 doi: 10.3390/ijms13044168. PMID: 22605972Free PMC Article

Diagnosis

Congenital Diarrhea and Enteropathies in Infants: Approach to Diagnosis.
Mantoo MR, Malik R, Das P, Yadav R, Nakra T, Chouhan P
Indian J Pediatr 2021 Nov;88(11):1135-1138. Epub 2021 Jul 22 doi: 10.1007/s12098-021-03844-z. PMID: 34292522
Literature review on congenital glucose-galactose malabsorption from 2001 to 2019.
Wang W, Wang L, Ma M
J Paediatr Child Health 2020 Nov;56(11):1779-1784. Epub 2020 Sep 18 doi: 10.1111/jpc.14702. PMID: 32946683
Sucrase-Isomaltase Deficiency as a Potential Masquerader in Irritable Bowel Syndrome.
Kim SB, Calmet FH, Garrido J, Garcia-Buitrago MT, Moshiree B
Dig Dis Sci 2020 Feb;65(2):534-540. Epub 2019 Sep 6 doi: 10.1007/s10620-019-05780-7. PMID: 31493040
Shwachman-Diamond syndrome: Nationwide survey and systematic review in Japan.
Ikuse T, Kudo T, Arai K, Fujii Y, Ida S, Ishii T, Mushiake S, Nagata K, Tamai H, Toki A, Tomomasa T, Ushijima K, Yanagi T, Yonekura T, Taguchi T, Shimizu T
Pediatr Int 2018 Aug;60(8):719-726. Epub 2018 Jul 10 doi: 10.1111/ped.13601. PMID: 29804317
Congenital intestinal diarrhoeal diseases: A diagnostic and therapeutic challenge.
Posovszky C
Best Pract Res Clin Gastroenterol 2016 Apr;30(2):187-211. Epub 2016 Mar 11 doi: 10.1016/j.bpg.2016.03.004. PMID: 27086885

Therapy

Congenital Glucose-Galactose Malabsorption: A Case Report.
Anderson S, Koniaris S, Xin B, Brooks SS
J Pediatr Health Care 2017 Jul-Aug;31(4):506-510. Epub 2017 Mar 7 doi: 10.1016/j.pedhc.2017.01.005. PMID: 28283348
Microvillous inclusion disease: how to improve the prognosis of a severe congenital enterocyte disorder.
Halac U, Lacaille F, Joly F, Hugot JP, Talbotec C, Colomb V, Ruemmele FM, Goulet O
J Pediatr Gastroenterol Nutr 2011 Apr;52(4):460-5. doi: 10.1097/MPG.0b013e3181fb4559. PMID: 21407114
Congenital selective malabsorption of glucose and galactose.
Evans L, Grasset E, Heyman M, Dumontier AM, Beau JP, Desjeux JF
J Pediatr Gastroenterol Nutr 1985 Dec;4(6):878-86. doi: 10.1097/00005176-198512000-00006. PMID: 4067775
Congenital folate malabsorption.
Corbeel L, Van den Berghe G, Jaeken J, Van Tornout J, Eeckels R
Eur J Pediatr 1985 Mar;143(4):284-90. doi: 10.1007/BF00442302. PMID: 3987728
Enterokinase and trypsin activities in pancreatic insufficiency and diseases of the small intestine.
Lebenthal E, Antonowicz I, Shwachman H
Gastroenterology 1976 Apr;70(4):508-12. PMID: 943355

Prognosis

Congenital Rare Diseases Causing Persistent Diarrhea in the Newborn: A Single Center Experience.
Hoşnut FÖ, Sahin GE, Ozyazıcı A, Olgac A, Aksu AU
Z Geburtshilfe Neonatol 2022 Oct;226(5):311-318. Epub 2022 May 16 doi: 10.1055/a-1774-5005. PMID: 35576965
Literature review on congenital glucose-galactose malabsorption from 2001 to 2019.
Wang W, Wang L, Ma M
J Paediatr Child Health 2020 Nov;56(11):1779-1784. Epub 2020 Sep 18 doi: 10.1111/jpc.14702. PMID: 32946683
Shwachman-Diamond syndrome: Nationwide survey and systematic review in Japan.
Ikuse T, Kudo T, Arai K, Fujii Y, Ida S, Ishii T, Mushiake S, Nagata K, Tamai H, Toki A, Tomomasa T, Ushijima K, Yanagi T, Yonekura T, Taguchi T, Shimizu T
Pediatr Int 2018 Aug;60(8):719-726. Epub 2018 Jul 10 doi: 10.1111/ped.13601. PMID: 29804317
Congenital Glucose-Galactose Malabsorption: A Case Report.
Anderson S, Koniaris S, Xin B, Brooks SS
J Pediatr Health Care 2017 Jul-Aug;31(4):506-510. Epub 2017 Mar 7 doi: 10.1016/j.pedhc.2017.01.005. PMID: 28283348
Intractable diarrhea of infancy: 10 years of experience.
Hizarcioglu-Gulsen H, Saltik-Temizel IN, Demir H, Gurakan F, Ozen H, Yuce A
J Pediatr Gastroenterol Nutr 2014 Nov;59(5):571-6. doi: 10.1097/MPG.0000000000000485. PMID: 25000351

Clinical prediction guides

Amelioration of Congenital Tufting Enteropathy in EpCAM (TROP1)-Deficient Mice via Heterotopic Expression of TROP2 in Intestinal Epithelial Cells.
Nakato G, Morimura S, Lu M, Feng X, Wu C, Udey MC
Cells 2020 Aug 6;9(8) doi: 10.3390/cells9081847. PMID: 32781650Free PMC Article
Congenital sucrase-isomaltase deficiency: identification of a common Inuit founder mutation.
Marcadier JL, Boland M, Scott CR, Issa K, Wu Z, McIntyre AD, Hegele RA, Geraghty MT, Lines MA
CMAJ 2015 Feb 3;187(2):102-107. Epub 2014 Dec 1 doi: 10.1503/cmaj.140657. PMID: 25452324Free PMC Article
Tufting enteropathy revisited: the utility of MOC31 (EpCAM) immunohistochemistry in diagnosis.
Ranganathan S, Schmitt LA, Sindhi R
Am J Surg Pathol 2014 Feb;38(2):265-72. doi: 10.1097/PAS.0000000000000106. PMID: 24418860
Enteroendocrine cell dysgenesis and malabsorption, a histopathologic and immunohistochemical characterization.
Cortina G, Smart CN, Farmer DG, Bhuta S, Treem WR, Hill ID, Martín MG
Hum Pathol 2007 Apr;38(4):570-80. Epub 2007 Jan 29 doi: 10.1016/j.humpath.2006.10.014. PMID: 17258790
Atypical findings in Kabuki syndrome: report of 8 patients in a series of 20 and review of the literature.
Geneviève D, Amiel J, Viot G, Le Merrer M, Sanlaville D, Urtizberea A, Gérard M, Munnich A, Cormier-Daire V, Lyonnet S
Am J Med Genet A 2004 Aug 15;129A(1):64-8. doi: 10.1002/ajmg.a.30144. PMID: 15266618

Recent systematic reviews

Genetic Enteropathies Linked to Epithelial Structural Abnormalities and Enteroendocrine Deficiency: A Systematic Review.
Caralli M, Roman C, Coste ME, Roquelaure B, Buffat C, Bourgeois P, Badens C, Fabre A
J Pediatr Gastroenterol Nutr 2021 Jun 1;72(6):826-832. doi: 10.1097/MPG.0000000000003049. PMID: 33976085
Shwachman-Diamond syndrome: Nationwide survey and systematic review in Japan.
Ikuse T, Kudo T, Arai K, Fujii Y, Ida S, Ishii T, Mushiake S, Nagata K, Tamai H, Toki A, Tomomasa T, Ushijima K, Yanagi T, Yonekura T, Taguchi T, Shimizu T
Pediatr Int 2018 Aug;60(8):719-726. Epub 2018 Jul 10 doi: 10.1111/ped.13601. PMID: 29804317

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