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Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives
Congenital lactase deficiency (CLD) is a severe autosomal recessive genetic disorder that affects the functional capacity of the intestinal protein lactase-phlorizin hydrolase (LPH). This disorder is diagnosed already during the first few days of the newborn’s life due to the inability to digest lac...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412902/ https://www.ncbi.nlm.nih.gov/pubmed/30813293 http://dx.doi.org/10.3390/nu11020461 |
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author | Wanes, Dalanda Husein, Diab M. Naim, Hassan Y. |
author_facet | Wanes, Dalanda Husein, Diab M. Naim, Hassan Y. |
author_sort | Wanes, Dalanda |
collection | PubMed |
description | Congenital lactase deficiency (CLD) is a severe autosomal recessive genetic disorder that affects the functional capacity of the intestinal protein lactase-phlorizin hydrolase (LPH). This disorder is diagnosed already during the first few days of the newborn’s life due to the inability to digest lactose, the main carbohydrate in mammalian milk. The symptoms are similar to those in other carbohydrate malabsorption disorders, such as congenital sucrase-isomaltase deficiency, and include severe osmotic watery diarrhea. CLD is associated with mutations in the translated region of the LPH gene that elicit loss-of-function of LPH. The mutations occur in a homozygote or compound heterozygote pattern of inheritance and comprise missense mutations as well as mutations that lead to complete or partial truncations of crucial domains in LPH, such as those linked to the folding and transport-competence of LPH and to the catalytic domains. Nevertheless, the identification of the mutations in CLD is not paralleled by detailed genotype/protein phenotype analyses that would help unravel potential pathomechanisms underlying this severe disease. Here, we review the current knowledge of CLD mutations and discuss their potential impact on the structural and biosynthetic features of LPH. We also address the question of whether heterozygote carriers can be symptomatic for CLD and whether genetic testing is needed in view of the severity of the disease. |
format | Online Article Text |
id | pubmed-6412902 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64129022019-04-09 Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives Wanes, Dalanda Husein, Diab M. Naim, Hassan Y. Nutrients Review Congenital lactase deficiency (CLD) is a severe autosomal recessive genetic disorder that affects the functional capacity of the intestinal protein lactase-phlorizin hydrolase (LPH). This disorder is diagnosed already during the first few days of the newborn’s life due to the inability to digest lactose, the main carbohydrate in mammalian milk. The symptoms are similar to those in other carbohydrate malabsorption disorders, such as congenital sucrase-isomaltase deficiency, and include severe osmotic watery diarrhea. CLD is associated with mutations in the translated region of the LPH gene that elicit loss-of-function of LPH. The mutations occur in a homozygote or compound heterozygote pattern of inheritance and comprise missense mutations as well as mutations that lead to complete or partial truncations of crucial domains in LPH, such as those linked to the folding and transport-competence of LPH and to the catalytic domains. Nevertheless, the identification of the mutations in CLD is not paralleled by detailed genotype/protein phenotype analyses that would help unravel potential pathomechanisms underlying this severe disease. Here, we review the current knowledge of CLD mutations and discuss their potential impact on the structural and biosynthetic features of LPH. We also address the question of whether heterozygote carriers can be symptomatic for CLD and whether genetic testing is needed in view of the severity of the disease. MDPI 2019-02-22 /pmc/articles/PMC6412902/ /pubmed/30813293 http://dx.doi.org/10.3390/nu11020461 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Wanes, Dalanda Husein, Diab M. Naim, Hassan Y. Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives |
title | Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives |
title_full | Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives |
title_fullStr | Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives |
title_full_unstemmed | Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives |
title_short | Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives |
title_sort | congenital lactase deficiency: mutations, functional and biochemical implications, and future perspectives |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412902/ https://www.ncbi.nlm.nih.gov/pubmed/30813293 http://dx.doi.org/10.3390/nu11020461 |
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