This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is congenital lactase deficiency?Congenital lactase deficiency, also known as congenital alactasia, is a severe, infant form of lactose intolerance characterized by the inability to properly digest lactose[1]. Individuals remain unable to digest lactose through adulthood. Lactose is a sugar present in milk (including cow's milk, goat's milk, sheep's milk, and breastmilk) and other dairy products. Lactose intolerance is not the same as having an allergy to milk [2]. The condition was first reported by Hozel et al. in 1959 in Finland[3]. Finland still reports significantly higher rates of congenital lactase deficiency than the worldwide occurrence rate. The rate of occurrence today is approximately 1:60000 births [4].
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How is lactose digested?
Lactose is a disaccharide, meaning it is a sugar made of two simple sugar subunits[10]. When sugars are digested, they are broken down into sugars that the body can use, which includes glucose and galactose. The lactase enzyme works by breaking the bond between the two subunits (glycosidic bond), causing the formation of one glucose and one galactose.
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What are the symptoms and treatments?
Infants who are given breast milk or formula that contains lactose will experience severe diarrhea. If this persists, it can result in dehydration and weight loss [5]. There is no cure for the disease, and little treatment [4]. There is currently, no way to make the body produce more functional lactase. However, to treat the symptoms, removing lactose from the diet usually results in full recovery, and maintaining a lactose-free diet usually mitigates any future symptoms.
What causes congenital lactose deficiency?Congenital lactose deficiency is caused by a mutation in the LCT gene. This gene contains the coding information to produce the lactase enzyme, which is responsible for lactose digestion. The mutation leads to either truncation of the protein or amino acid substitutions in the protein both of which inhibit the function of lactase [4].
How is it inherited?This is an autosomal recessive disease. This means that each parent was a carrier and had one copy of the mutation (Figure 1). Since the disease is recessive, having only one mutant copy does not cause the disease. The child inherited one mutant copy from each parent, resulting in two mutant copies which causes congenital lactase deficiency.
Additionally, there has been a recent case reported in which a child inherited compound heterozygous mutations in the LCT gene [9]. This means that each parent had a different mutation in the LCT, each of which individually did not cause symptoms. However, each parent passed his/her mutation to the child, resulting in CLD. |
What is LCT?
LCT is the gene which causes lactose intolerance. LCT is responsible for the production of a functioning lactase enzyme. This gene is located on the long arm of chromosome 2 at position 21 (2q21) (Figure 2) [3]. This enzyme digests lactose by breaking it down into sugars that the body can absorb, specifically: glucose and galactose. Congenital lactose deficiency is caused by the inheritance of two recessive mutations within the LCT gene itself. This mutation results in the malfunction of the lactase enzyme, by amino acid substitutions (missense mutations) or premature truncation (nonsense mutations) [4]. Adult lactose intolerance (lactase non-persistence) is caused by the decreased expression of the LCT gene, which results in decreased production of lactase enzyme. This form of lactose intolerance is caused by a mutation in an upstream regulator of LCT, and not a mutation within LCT itself [6].
It remains unclear exactly how many different mutations within LCT cause congenital lactase deficiency, as well as the differential effects of mutations that occur in different locations throughout the gene. There are currently at least seven known mutations within the LCT gene itself, including the founder mutation traced from the original Finnish population, all of which result in similar phenotypes [7, 8]. Additionally, it is unknown what might cause a predisposition to mutations in the LCT gene in certain populations.
It remains unclear exactly how many different mutations within LCT cause congenital lactase deficiency, as well as the differential effects of mutations that occur in different locations throughout the gene. There are currently at least seven known mutations within the LCT gene itself, including the founder mutation traced from the original Finnish population, all of which result in similar phenotypes [7, 8]. Additionally, it is unknown what might cause a predisposition to mutations in the LCT gene in certain populations.
Who else is interested in congenital lactose deficiency?
About me
Hayley Stoneman
Genetics and Genomics, UW-Madison
[email protected]
Genetics564 Website
Page last updated: 5/2/19
Genetics and Genomics, UW-Madison
[email protected]
Genetics564 Website
Page last updated: 5/2/19
References
[1] Genetics Home Reference (2019). Lactose Intolerance. U.S. National Library of Medicine. Retrieved from https://ghr.nlm.nih.gov/condition/lactose-intolerance#genes
[2] Health Library (n.d.). Lactose Intolerance. Johns Hopkins Medicine. Retrieved from https://www.hopkinsmedicine.org/healthlibrary/conditions/digestive_disorders/lactose_intolerance_85,P00388
[3] Mattar, R. et al. (2012, July). Lactose intolerance: diagnosis, genetics, and clinical factors. Clinical and Experimental Gastrology. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401057/
[4] Kuokkanen, M. et. al. (2006, February). Mutations in the Translated Region of the Lactase Gene (LCT) Underlie Congenital Lactase Deficiency. American Journal on Human Genetics. Retrieved from https://www.sciencedirect.com/science/article/pii/S0002929707623647
[5] Hozel, A. et al. (1959, May). Defective Lactose Absorption Causing Malnutrition in Infancy. The Lancet. Retrieved from https://www.sciencedirect.com/science/article/pii/S014067365990710X?via%3Dihub
[6] Khaborova, y. et al. (2010, September). The -13914G>A variant upstream of the lactase gene (LCT) is associated with lactase persistence/non-persistence. Scandinavian Journal of Clinical and Laboratory Investigation. Retrieved from www.ncbi.nlm.nih.gov/pubmed/20509822
[7] Torniainen, S. et al. (2009, January). Four novel mutations in the lactase gene (LCT) underlying congenital lactase deficiency (CLD). BMC Gastroenterology. Retrieved from www.ncbi.nlm.nih.gov/pubmed/19161632
[8] Uchida, N. et al. (2012). Two Novel Mutations in the Lactase Gene in a Japanese Infant with Congenital Lactase Deficiency. The Tohoku Journal of Experimental Medicine. Retrieved from www.jstage.jst.go.jp/article/tjem/227/1/227_69/_article/-char/ja/
[9] Diekmann, L et al. (2015, March). Congenital lactose intolerance is triggered by severe mutations on both alleles of the lactase gene. BMC Gastroenterology. Retrieved from bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-015-0261-y
[10] Paine, E. (2016, September). The Science Behind Lactose Intolerance. www.carolina.com/teacher-resources/Interactive/the-science-behind-lactose-intolerance/tr38902.tr
Header image
[1] http://fortune.com/2017/03/07/crowd-cow-beef-crowdsourcing/
[2] Health Library (n.d.). Lactose Intolerance. Johns Hopkins Medicine. Retrieved from https://www.hopkinsmedicine.org/healthlibrary/conditions/digestive_disorders/lactose_intolerance_85,P00388
[3] Mattar, R. et al. (2012, July). Lactose intolerance: diagnosis, genetics, and clinical factors. Clinical and Experimental Gastrology. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401057/
[4] Kuokkanen, M. et. al. (2006, February). Mutations in the Translated Region of the Lactase Gene (LCT) Underlie Congenital Lactase Deficiency. American Journal on Human Genetics. Retrieved from https://www.sciencedirect.com/science/article/pii/S0002929707623647
[5] Hozel, A. et al. (1959, May). Defective Lactose Absorption Causing Malnutrition in Infancy. The Lancet. Retrieved from https://www.sciencedirect.com/science/article/pii/S014067365990710X?via%3Dihub
[6] Khaborova, y. et al. (2010, September). The -13914G>A variant upstream of the lactase gene (LCT) is associated with lactase persistence/non-persistence. Scandinavian Journal of Clinical and Laboratory Investigation. Retrieved from www.ncbi.nlm.nih.gov/pubmed/20509822
[7] Torniainen, S. et al. (2009, January). Four novel mutations in the lactase gene (LCT) underlying congenital lactase deficiency (CLD). BMC Gastroenterology. Retrieved from www.ncbi.nlm.nih.gov/pubmed/19161632
[8] Uchida, N. et al. (2012). Two Novel Mutations in the Lactase Gene in a Japanese Infant with Congenital Lactase Deficiency. The Tohoku Journal of Experimental Medicine. Retrieved from www.jstage.jst.go.jp/article/tjem/227/1/227_69/_article/-char/ja/
[9] Diekmann, L et al. (2015, March). Congenital lactose intolerance is triggered by severe mutations on both alleles of the lactase gene. BMC Gastroenterology. Retrieved from bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-015-0261-y
[10] Paine, E. (2016, September). The Science Behind Lactose Intolerance. www.carolina.com/teacher-resources/Interactive/the-science-behind-lactose-intolerance/tr38902.tr
Header image
[1] http://fortune.com/2017/03/07/crowd-cow-beef-crowdsourcing/