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Nonpersistence of intestinal lactase

MedGen UID:
75659
Concept ID:
C0268181
Disease or Syndrome
Synonyms: ADULT LACTASE DEFICIENCY; DISACCHARIDE INTOLERANCE III; HYPOLACTASIA, ADULT TYPE; Lactose intolerance, adult type
SNOMED CT: Ontogenic late onset lactase deficiency (38032004); Non-persistence of intestinal lactase (38032004); Adult lactase deficiency (38032004); Late onset lactase deficiency (38032004); Nonpersistence of intestinal lactase (38032004); Delayed-onset isolated lactase deficiency (38032004); Late-onset lactose intolerance (38032004); Disaccharide intolerance III (38032004); Primary hypolactasia (38032004)
 
Gene (location): MCM6 (2q21.3)
 
Monarch Initiative: MONDO:0006065
OMIM®: 223100
Orphanet: ORPHA319681

Definition

In humans, the activities of lactase and most of the other digestive hydrolases are maximal at birth. The majority of the world's human population experiences a decline in production of the digestive enzyme lactase-phlorizin hydrolase during maturation, with the age of onset ranging from the toddler years to young adulthood. Due to the reduced lactase level, lactose present in dairy products cannot be digested in the small intestine and instead is fermented by bacteria in the distal ileum and colon. The fermentative products result in symptoms of diarrhea, gas bloat, flatulence, and abdominal pain. However, in a minority of adults, high levels of lactase activity persist in adulthood. Lactase persistence is a heritable autosomal dominant condition that results in a sustained ability to digest the milk sugar lactose throughout adulthood (Olds and Sibley, 2003). [from OMIM]

Additional description

From MedlinePlus Genetics
Lactose intolerance in adulthood can be caused by the reduced production of lactase after infancy (lactase nonpersistence). If individuals with lactose intolerance consume lactose-containing dairy products, they may experience abdominal pain, bloating, flatulence, nausea, and diarrhea beginning 30 minutes to 2 hours later.

Congenital lactase deficiency, also called congenital alactasia, is a disorder in which infants are unable to break down the lactose in breast milk or formula. This form of lactose intolerance results in very severe diarrhea. If affected infants are not given a lactose-free infant formula, they may experience severe dehydration and weight loss.

Lactose intolerance is a condition that makes it difficult to digest lactose, a sugar found in milk and several other dairy products. Lactose is normally broken down by an enzyme called lactase, which is produced by cells in the lining of the small intestine. Lack or loss of lactase has both genetic and non-genetic causes.

Most people with lactase nonpersistence retain some lactase activity and can include varying amounts of lactose in their diets without experiencing symptoms. Often, affected individuals have difficulty digesting fresh milk but can eat certain dairy products such as cheese or yogurt without discomfort. These foods are made using fermentation processes that break down much of the lactose in milk.  https://medlineplus.gov/genetics/condition/lactose-intolerance

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
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.
Flatulence
MedGen UID:
5208
Concept ID:
C0016204
Sign or Symptom
Passage of excessive amounts of gas and the feeling of abdominal fullness and bloating.
Lactose intolerance
MedGen UID:
6001
Concept ID:
C0022951
Disease or Syndrome
An inability to digest lactose.
Decreased small intestinal mucosa lactase level
MedGen UID:
1390950
Concept ID:
C4476604
Finding
Lactase is produced in the small intestine in humans, Lactase is a member of the beta-galactosidase family of enzymes, and hydrolyzes D-lactose to form D-galactose and D-glucose, which can be absorbed by the small intestine. There are many ways of assessing lactase activity. In one test, an endoscopic biopsy from the postbulbar duodenum is incubated with lactose on a test plate, and a color reaction develops within 20 min as a result of hydrolyzed lactose (a positive result) in patients with normolactasia, whereas no reaction (a negative result) develops in patients with severe hypolactasia. Other, less direct, tests include the hydrogen breath test, and blood tests following lactose challenges.

Professional guidelines

PubMed

Nagy D, Bogácsi-Szabó E, Várkonyi A, Csányi B, Czibula A, Bede O, Tari B, Raskó I
Eur J Clin Nutr 2009 Jul;63(7):909-12. Epub 2009 Jan 21 doi: 10.1038/ejcn.2008.74. PMID: 19156157
Schirru E, Corona V, Usai-Satta P, Scarpa M, Oppia F, Loriga F, Cucca F, De Virgiliis S, Rossino R, Macis MD, Jores RD, Congia M
Eur J Clin Nutr 2007 Oct;61(10):1220-5. Epub 2007 Feb 21 doi: 10.1038/sj.ejcn.1602638. PMID: 17311063
Montalto M, Curigliano V, Santoro L, Vastola M, Cammarota G, Manna R, Gasbarrini A, Gasbarrini G
World J Gastroenterol 2006 Jan 14;12(2):187-91. doi: 10.3748/wjg.v12.i2.187. PMID: 16482616Free PMC Article

Recent clinical studies

Etiology

Leseva MN, Grand RJ, Klett H, Boerries M, Busch H, Binder AM, Michels KB
Sci Rep 2018 Apr 4;8(1):5649. doi: 10.1038/s41598-018-23957-4. PMID: 29618745Free PMC Article
Szilagyi A
Can J Gastroenterol Hepatol 2015 Apr;29(3):149-56. doi: 10.1155/2015/904686. PMID: 25855879Free PMC Article
Shrier I, Szilagyi A, Correa JA
Nutr Cancer 2008;60(3):292-300. doi: 10.1080/01635580701745301. PMID: 18444163
Montgomery RK, Krasinski SD, Hirschhorn JN, Grand RJ
J Pediatr Gastroenterol Nutr 2007 Dec;45 Suppl 2:S131-7. doi: 10.1097/MPG.0b013e31812e68f6. PMID: 18185074
Järvelä IE
Ann Med 2005;37(3):179-85. doi: 10.1080/07853890510007359. PMID: 16019716

Diagnosis

Szilagyi A
Can J Gastroenterol Hepatol 2015 Apr;29(3):149-56. doi: 10.1155/2015/904686. PMID: 25855879Free PMC Article
Lomer MC, Parkes GC, Sanderson JD
Aliment Pharmacol Ther 2008 Jan 15;27(2):93-103. Epub 2007 Oct 23 doi: 10.1111/j.1365-2036.2007.03557.x. PMID: 17956597
Enattah NS, Kuokkanen M, Forsblom C, Natah S, Oksanen A, Jarvela I, Peltonen L, Savilahti E
World J Gastroenterol 2007 Jul 7;13(25):3508-12. doi: 10.3748/wjg.v13.i25.3508. PMID: 17659699Free PMC Article
Schirru E, Corona V, Usai-Satta P, Scarpa M, Oppia F, Loriga F, Cucca F, De Virgiliis S, Rossino R, Macis MD, Jores RD, Congia M
Eur J Clin Nutr 2007 Oct;61(10):1220-5. Epub 2007 Feb 21 doi: 10.1038/sj.ejcn.1602638. PMID: 17311063
Sibley E
Am J Pharmacogenomics 2004;4(4):239-45. doi: 10.2165/00129785-200404040-00003. PMID: 15287817

Therapy

Vionnet N, Münger LH, Freiburghaus C, Burton KJ, Pimentel G, Pralong FP, Badertscher R, Vergères G
Am J Clin Nutr 2019 Feb 1;109(2):470-477. doi: 10.1093/ajcn/nqy296. PMID: 30721917Free PMC Article
Perino A, Cabras S, Obinu D, Cavalli Sforza L
Eur Ann Allergy Clin Immunol 2009 Feb;41(1):3-16. PMID: 19496347
Lomer MC, Parkes GC, Sanderson JD
Aliment Pharmacol Ther 2008 Jan 15;27(2):93-103. Epub 2007 Oct 23 doi: 10.1111/j.1365-2036.2007.03557.x. PMID: 17956597
Torniainen S, Hedelin M, Autio V, Rasinperä H, Bälter KA, Klint A, Bellocco R, Wiklund F, Stattin P, Ikonen T, Tammela TL, Schleutker J, Grönberg H, Järvelä I
Cancer Epidemiol Biomarkers Prev 2007 May;16(5):956-61. doi: 10.1158/1055-9965.EPI-06-0985. PMID: 17507622
Montalto M, Curigliano V, Santoro L, Vastola M, Cammarota G, Manna R, Gasbarrini A, Gasbarrini G
World J Gastroenterol 2006 Jan 14;12(2):187-91. doi: 10.3748/wjg.v12.i2.187. PMID: 16482616Free PMC Article

Prognosis

Leseva MN, Grand RJ, Klett H, Boerries M, Busch H, Binder AM, Michels KB
Sci Rep 2018 Apr 4;8(1):5649. doi: 10.1038/s41598-018-23957-4. PMID: 29618745Free PMC Article
Baffour-Awuah NY, Fleet S, Montgomery RK, Baker SS, Butler JL, Campbell C, Tischfield S, Mitchell PD, Allende-Richter S, Moon JE, Fishman L, Bousvaros A, Fox V, Kuokkanen M, Grand RJ, Hirschhorn JN
J Pediatr Gastroenterol Nutr 2015 Feb;60(2):182-91. doi: 10.1097/MPG.0000000000000595. PMID: 25625576Free PMC Article
Nagy D, Bogácsi-Szabó E, Várkonyi A, Csányi B, Czibula A, Bede O, Tari B, Raskó I
Eur J Clin Nutr 2009 Jul;63(7):909-12. Epub 2009 Jan 21 doi: 10.1038/ejcn.2008.74. PMID: 19156157
Schirru E, Corona V, Usai-Satta P, Scarpa M, Oppia F, Loriga F, Cucca F, De Virgiliis S, Rossino R, Macis MD, Jores RD, Congia M
Eur J Clin Nutr 2007 Oct;61(10):1220-5. Epub 2007 Feb 21 doi: 10.1038/sj.ejcn.1602638. PMID: 17311063
Rasinperä H, Savilahti E, Enattah NS, Kuokkanen M, Tötterman N, Lindahl H, Järvelä I, Kolho KL
Gut 2004 Nov;53(11):1571-6. doi: 10.1136/gut.2004.040048. PMID: 15479673Free PMC Article

Clinical prediction guides

Segurel L, Guarino-Vignon P, Marchi N, Lafosse S, Laurent R, Bon C, Fabre A, Hegay T, Heyer E
PLoS Biol 2020 Jun;18(6):e3000742. Epub 2020 Jun 8 doi: 10.1371/journal.pbio.3000742. PMID: 32511234Free PMC Article
Vionnet N, Münger LH, Freiburghaus C, Burton KJ, Pimentel G, Pralong FP, Badertscher R, Vergères G
Am J Clin Nutr 2019 Feb 1;109(2):470-477. doi: 10.1093/ajcn/nqy296. PMID: 30721917Free PMC Article
Leseva MN, Grand RJ, Klett H, Boerries M, Busch H, Binder AM, Michels KB
Sci Rep 2018 Apr 4;8(1):5649. doi: 10.1038/s41598-018-23957-4. PMID: 29618745Free PMC Article
Enattah NS, Kuokkanen M, Forsblom C, Natah S, Oksanen A, Jarvela I, Peltonen L, Savilahti E
World J Gastroenterol 2007 Jul 7;13(25):3508-12. doi: 10.3748/wjg.v13.i25.3508. PMID: 17659699Free PMC Article
Potter J, Ho MW, Bolton H, Furth AJ, Swallow DM, Griffiths B
Biochem Genet 1985 Jun;23(5-6):423-39. doi: 10.1007/BF00499084. PMID: 3929764

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