Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wanes, Dalanda, Husein, Diab M., Naim, Hassan Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783402713728417792
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
work_keys_str_mv AT wanesdalanda congenitallactasedeficiencymutationsfunctionalandbiochemicalimplicationsandfutureperspectives
AT huseindiabm congenitallactasedeficiencymutationsfunctionalandbiochemicalimplicationsandfutureperspectives
AT naimhassany congenitallactasedeficiencymutationsfunctionalandbiochemicalimplicationsandfutureperspectives