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Congenital lactase deficiency

MedGen UID:
120617
Concept ID:
C0268179
Disease or Syndrome
Synonyms: ALACTASIA, CONGENITAL; DISACCHARIDE INTOLERANCE II
SNOMED CT: Congenital lactase deficiency (5388008); Congenital lactose intolerance (5388008); Congenital lactose malabsorption (5388008); Congenital alactasia syndrome (5388008); Disaccharide intolerance II (5388008); Congenital alactasia (5388008); CLD - Congenital lactase deficiency (5388008)
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): LCT (2q21.3)
 
Monarch Initiative: MONDO:0009115
OMIM®: 223000
Orphanet: ORPHA53690

Definition

Congenital lactase deficiency is a severe gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. [from OMIM]

Additional description

From MedlinePlus Genetics
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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/lactose-intolerance

Clinical features

From HPO
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.
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.
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.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.

Term Hierarchy

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

Professional guidelines

PubMed

Bortot B, De Martino E, Tesser A, Ura B, Ruozi B, Aloisio M, Biffi S, Addobbati R, Tosi G, Dolcetta D, Severini GM
Int J Mol Med 2019 Jul;44(1):262-272. Epub 2019 May 16 doi: 10.3892/ijmm.2019.4199. PMID: 31115488

Recent clinical studies

Etiology

Seoane RG, Garcia-Recio V, Garrosa M, Rojo MÁ, Jiménez P, Girbés T, Cordoba-Diaz M, Cordoba-Diaz D
Curr Pharm Des 2020;26(16):1778-1789. doi: 10.2174/1381612826666200212114843. PMID: 32048961
Siddiqui Z, Osayande AS
Prim Care 2011 Sep;38(3):395-414; vii. doi: 10.1016/j.pop.2011.05.002. PMID: 21872088
O'Connor NR
Am Fam Physician 2009 Apr 1;79(7):565-70. PMID: 19378873
Savilahti E, Launiala K, Kuitunen P
Arch Dis Child 1983 Apr;58(4):246-52. doi: 10.1136/adc.58.4.246. PMID: 6847226Free PMC Article
Bayless TM, Christopher NL
Am J Clin Nutr 1969 Feb;22(2):181-90. doi: 10.1093/ajcn/22.2.181. PMID: 4885929

Diagnosis

Seoane RG, Garcia-Recio V, Garrosa M, Rojo MÁ, Jiménez P, Girbés T, Cordoba-Diaz M, Cordoba-Diaz D
Curr Pharm Des 2020;26(16):1778-1789. doi: 10.2174/1381612826666200212114843. PMID: 32048961
Wanes D, Husein DM, Naim HY
Nutrients 2019 Feb 22;11(2) doi: 10.3390/nu11020461. PMID: 30813293Free PMC Article
Vandenplas Y
Asia Pac J Clin Nutr 2015;24 Suppl 1:S9-13. doi: 10.6133/apjcn.2015.24.s1.02. PMID: 26715083
Robayo-Torres CC, Nichols BL
Nutr Rev 2007 Feb;65(2):95-8. doi: 10.1111/j.1753-4887.2007.tb00286.x. PMID: 17345962
Savilahti E, Launiala K, Kuitunen P
Arch Dis Child 1983 Apr;58(4):246-52. doi: 10.1136/adc.58.4.246. PMID: 6847226Free PMC Article

Therapy

Vandenplas Y
Asia Pac J Clin Nutr 2015;24 Suppl 1:S9-13. doi: 10.6133/apjcn.2015.24.s1.02. PMID: 26715083
Uchida N, Sakamoto O, Irie M, Abukawa D, Takeyama J, Kure S, Tsuchiya S
Tohoku J Exp Med 2012 May;227(1):69-72. doi: 10.1620/tjem.227.69. PMID: 22688420
Villako K, Maaroos H
Scand J Gastroenterol Suppl 1994;202:36-54. doi: 10.3109/00365529409091743. PMID: 8042017
Kuitunen P, Kosnai I, Savilahti E
J Pediatr Gastroenterol Nutr 1982;1(4):525-31. doi: 10.1097/00005176-198212000-00012. PMID: 7186067
Similä S, Kokkonen J, Kouvalainen K
J Pediatr 1982 Oct;101(4):584-5. doi: 10.1016/s0022-3476(82)80712-9. PMID: 7119963

Prognosis

de Leusse C, Roman C, Roquelaure B, Fabre A
Arch Pediatr 2022 Nov;29(8):599-603. Epub 2022 Sep 25 doi: 10.1016/j.arcped.2022.08.005. PMID: 36167617
Torniainen S, Freddara R, Routi T, Gijsbers C, Catassi C, Höglund P, Savilahti E, Järvelä I
BMC Gastroenterol 2009 Jan 22;9:8. doi: 10.1186/1471-230X-9-8. PMID: 19161632Free PMC Article
Kuokkanen M, Kokkonen J, Enattah NS, Ylisaukko-Oja T, Komu H, Varilo T, Peltonen L, Savilahti E, Jarvela I
Am J Hum Genet 2006 Feb;78(2):339-44. Epub 2005 Dec 15 doi: 10.1086/500053. PMID: 16400612Free PMC Article
Savilahti E, Launiala K, Kuitunen P
Arch Dis Child 1983 Apr;58(4):246-52. doi: 10.1136/adc.58.4.246. PMID: 6847226Free PMC Article
Kuitunen P, Kosnai I, Savilahti E
J Pediatr Gastroenterol Nutr 1982;1(4):525-31. doi: 10.1097/00005176-198212000-00012. PMID: 7186067

Clinical prediction guides

de Leusse C, Roman C, Roquelaure B, Fabre A
Arch Pediatr 2022 Nov;29(8):599-603. Epub 2022 Sep 25 doi: 10.1016/j.arcped.2022.08.005. PMID: 36167617
Torniainen S, Freddara R, Routi T, Gijsbers C, Catassi C, Höglund P, Savilahti E, Järvelä I
BMC Gastroenterol 2009 Jan 22;9:8. doi: 10.1186/1471-230X-9-8. PMID: 19161632Free PMC Article
Kuokkanen M, Kokkonen J, Enattah NS, Ylisaukko-Oja T, Komu H, Varilo T, Peltonen L, Savilahti E, Jarvela I
Am J Hum Genet 2006 Feb;78(2):339-44. Epub 2005 Dec 15 doi: 10.1086/500053. PMID: 16400612Free PMC Article
Rossi E, Lentze MJ
Ann Allergy 1984 Dec;53(6 Pt 2):649-56. PMID: 6439079

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