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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).
 
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.
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.
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.
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.
Hyperchloremic metabolic acidosis
MedGen UID:
369924
Concept ID:
C1969073
Disease or Syndrome
A form of metabolic acidosis with increased serum chloride levels.

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

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

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
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
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
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
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

Danialifar TF, Chumpitazi BP, Mehta DI, Di Lorenzo C
J Pediatr Gastroenterol Nutr 2024 Apr;78(4):774-782. Epub 2024 Feb 8 doi: 10.1002/jpn3.12151. PMID: 38327254
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
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
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
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

Therapy

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
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
Lücke T, Keiser M, Illsinger S, Lentze MJ, Naim HY, Das AM
J Pediatr Gastroenterol Nutr 2009 Oct;49(4):485-7. doi: 10.1097/MPG.0b013e3181a4c0df. PMID: 19680155
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
Lebenthal E, Antonowicz I, Shwachman H
Gastroenterology 1976 Apr;70(4):508-12. PMID: 943355

Prognosis

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
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
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
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
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

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
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
Ranganathan S, Schmitt LA, Sindhi R
Am J Surg Pathol 2014 Feb;38(2):265-72. doi: 10.1097/PAS.0000000000000106. PMID: 24418860
Chen CP, Chiang MC, Wang TH, Hsueh C, Chang SD, Tsai FJ, Wang CN, Chern SR, Wang W
Taiwan J Obstet Gynecol 2010 Dec;49(4):487-94. doi: 10.1016/S1028-4559(10)60102-7. PMID: 21199752
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

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
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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