Molecular basis of the main forms of congenital diarrheal diseases

Disease	Gene	Location	Function
Defects of digestion, absorption, and transport of nutrients and electrolytes
Disaccharidase deficiency
Congenital lactase deficiency	LCT	2q21	Lactase-phlorizin hydrolase activity
Sucrase-isomaltase deficiency	EC 3.2.1.48	3q25-q26	Isomaltase-sucrase
Maltase-glucoamylase deficiency	MGAM	7q34	Maltase-glucoamylase activity
Ion and nutrient transport defects
Glucose-galactose malabsorption	SLC5A1 (SGLT1)	22q13.1	Na⁺/glucose cotransporter
Fructose malabsorption	GLUT5	1p36	Fructose transporter
Fanconi-Bickel syndrome	GLUT2	3q26	Basolateral glucose transporter
Cystic fibrosis	CFTR	7q31.2	cAMP-dependent Cl^– channel
Acrodermatitis enteropathica	SLC39A4	8q24.3	Zn²⁺ transporter
Congenital chloride diarrhea	SLC26A3 (DRA)	7q22-q31.1	Cl^–/base exchanger
Congenital sodium diarrhea	SPINT2*	19q13.1	Serine-protease inhibitor
Familial diarrhea syndrome^[1]	GUCY2C	12p12.3	Intestinal guanylate cyclase C (ligand for bacterial heat-stable enterotoxins)
Lysinuric protein intolerance	SLC7A7	14q11	Hydrolyzes endo-/exopeptidases, amino acid basolateral transport
Congenital bile acid diarrhea	SLC10A2 (ABAT)	13q33	Ileal Na⁺/bile salt transporter
Pancreatic insufficiency
Enterokinase deficiency	PRSS7	21q21	Proenterokinase
Trypsinogen deficiency	PRSS1	7q35	Trypsinogen synthesis
Pancreatic lipase deficiency	PNLIP	10q26.1	Hydrolyzes triglycerides to fatty acids
Lipid trafficking
Abetalipoproteinemia	MTP	4q22	Transfer lipids to apolipoprotein B
Hypobetalipoproteinemia	APOB	2p24	Apolipoprotein that forms chylomicrons
Chylomicron retention disease	SAR1B	5q31.1	Intracellular chylomicron trafficking
Diacylglycerol acyltransferase 1 deficiency^[2]	DGAT1	8q24.3	Enzyme that catalyzes the final step in triglyceride synthesis
Defects of enterocyte differentiation and polarization
Microvillous inclusion disease	MY05B	18q21	Intracellular protein trafficking
Congenital tufting enteropathy	EpCAM	2p21	Cell-cell interaction
Syndromic diarrhea	Unknown	Unknown	Unknown
Defects of enteroendocrine cell differentiation
Enteric anendocrinosis	NEUROG3	10q21.3	Enteroendocrine cell fate determination
Enteric dysendocrinosis	Unknown	Unknown	Enteroendocrine cell function
Proprotein convertase 1 deficiency	PCSK1	5q15-q21	Prohormone processing
Defects of modulation of the intestinal immune response
IPEX	FOXP3	Xp11.23-q13.3	Transcription factor
IPEX-like syndrome	Unknown	Unknown	Unknown
Immunodeficiency-associated autoimmune enteropathy	Unknown	Unknown	Unknown
APS-1	AIRE	21p22.3	Regulation gene transcription
Autoimmune enteropathy with colitis-GAGD	Unknown	Unknown	Unknown

cAMP: cyclic adenosine monophosphate; EpCAM: epithelial cell adhesion molecule; NEUROG-3: neurogenin-3; IPEX: immune dysregulation polyendocrinopathy, enteropathy, X-linked syndrome; FOXP3: forkhead box P3; APS-1: autoimmune polyglandular syndrome-1; GAGD: generalized autoimmune gut disorder.
* This mutation has been associated with the syndromic form of congenital sodium diarrhea.

Reference:

Fikerstrand T, Arshad J, Haukanes BI, et al. Familial diarrhea syndrome caused by an activating GUCY2C mutation. New Engl J Med 2012; 366:1586.
Haas JT, Winter HS, Lim E, et al. DGAT1 mutation is linked to a congenital diarrheal disorder. J Clin Invest 2012; 122:4680.

All other entries in this table were reproduced with permission from: Canani RB, Terrin G, Cardillo G, et al. Congenital Diarrheal Disorders: Improved Understanding of Gene Disorders is Leading to Advances in Intestinal Physiology and Clinical Management. J Pediatr Gastroenterol Nutr 2010; 50:360. Copyright © 2010 Lippincott Williams & Wilkins.

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Molecular basis of the main forms of congenital diarrheal diseases