Molecular basis of erythroenzymopathies associated with hereditary hemolytic anemia: tabulation of mutant enzymes
- PMID:8579052
- DOI: 10.1002/(SICI)1096-8652(199602)51:2<122::AID-AJH5>3.0.CO;2-#
Molecular basis of erythroenzymopathies associated with hereditary hemolytic anemia: tabulation of mutant enzymes
Abstract
Molecular abnormalities of erythroenzymopathies associated with hereditary hemolytic anemia have been determined by means of molecular biology. Pyruvate kinase (PK) deficiency is the most common and well-characterized enzyme deficiency in the glycolytic pathway, and it causes hereditary hemolytic anemia. To date, 47 gene mutations have been identified. We identified one base deletion, one splicing mutation, and six distinct missense mutations in 12 unrelated families with a homozygous PK deficiency. Mutations located near the substrate or fructose-1,6- diphosphate binding site may change the conformation of the active site, resulting in a drastic loss of activity and severe clinical symptoms. Glucose-6-phosphate dehydrogenase (G6PD)deficiency is the most common metabolic disorder, and it is associated with chronic hemolytic anemia and/or drug- or infection-induced acute hemolytic attack. An estimated 400 million people are affected worldwide. The mutations responsible for about 78 variants have been determined. Some have polymorphic frequencies in different populations. Most variants are produced by one or two nucleotide substitutions. Molecular studies have disclosed that most of the class 1 G6PD variants associated with chronic hemolysis have the mutations surrounding either the substrate or the NADP binding site. Among rare enzymopathies, missense mutations have been determined in deficiencies of glucosephosphate isomerase, (TPI), phosphoglycerate kinase, and adenylate kinase. Compound heterozygosity with missense mutation and base deletion has been determined in deficiencies of hexokinase and diphosphoglyceromutase. Compound heterozygosity with missense and nonsense mutations has been identified in TPI deficiency. One base junction mutations resulting in abnormally spliced PFK-M mRNA have been identified in homozygous PFK deficiency. An exception is hemolytic anemia due to increased adenosine deaminase activity. The basic abnormality appears to result from the overproduction of a structurally normal enzyme.
Similar articles
- Red cell enzymopathies as a model of inborn errors of metabolism.Miwa S, Kanno H, Hirono A, Fujii H.Miwa S, et al.Southeast Asian J Trop Med Public Health. 1995;26 Suppl 1:112-9.Southeast Asian J Trop Med Public Health. 1995.PMID:8629088Review.
- [Pathophysiology and laboratory tests of hemolytic anemia: with special reference to erythroenzymopathies].Fujii H, Miwa S.Fujii H, et al.Rinsho Byori. 1989 Dec;37(12):1331-43.Rinsho Byori. 1989.PMID:2693773Review.Japanese.
- [Glucose-6-phosphate dehydrogenase].Fujii H.Fujii H.Nihon Rinsho. 1995 May;53(5):1221-5.Nihon Rinsho. 1995.PMID:7602782Review.Japanese.
- Molecular aspects of erythroenzymopathies associated with hereditary hemolytic anemia.Miwa S, Fujii H.Miwa S, et al.Am J Hematol. 1985 Jul;19(3):293-305. doi: 10.1002/ajh.2830190313.Am J Hematol. 1985.PMID:2990202Review.
- Spectrum of novel mutations in the human PKLR gene in pyruvate kinase-deficient Indian patients with heterogeneous clinical phenotypes.Kedar P, Hamada T, Warang P, Nadkarni A, Shimizu K, Fujji H, Ghosh K, Kanno H, Colah R.Kedar P, et al.Clin Genet. 2009 Feb;75(2):157-62. doi: 10.1111/j.1399-0004.2008.01079.x. Epub 2008 Aug 28.Clin Genet. 2009.PMID:18759866
Cited by
- Allogeneic hematopoietic stem cell transplantation in a 3-year-old boy with congenital pyruvate kinase deficiency: A case report.Ma ZY, Yang X.Ma ZY, et al.World J Clin Cases. 2021 Apr 26;9(12):2916-2922. doi: 10.12998/wjcc.v9.i12.2916.World J Clin Cases. 2021.PMID:33969077Free PMC article.
- Worldwide study of hematopoietic allogeneic stem cell transplantation in pyruvate kinase deficiency.van Straaten S, Bierings M, Bianchi P, Akiyoshi K, Kanno H, Serra IB, Chen J, Huang X, van Beers E, Ekwattanakit S, Güngör T, Kors WA, Smiers F, Raymakers R, Yanez L, Sevilla J, van Solinge W, Segovia JC, van Wijk R.van Straaten S, et al.Haematologica. 2018 Feb;103(2):e82-e86. doi: 10.3324/haematol.2017.177857. Epub 2017 Dec 14.Haematologica. 2018.PMID:29242305Free PMC article.No abstract available.
- From chemoproteomic-detected amino acids to genomic coordinates: insights into precise multi-omic data integration.Palafox MF, Desai HS, Arboleda VA, Backus KM.Palafox MF, et al.Mol Syst Biol. 2021 Feb;17(2):e9840. doi: 10.15252/msb.20209840.Mol Syst Biol. 2021.PMID:33599394Free PMC article.
- Alu element insertion in PKLR gene as a novel cause of pyruvate kinase deficiency in Middle Eastern patients.Lesmana H, Dyer L, Li X, Denton J, Griffiths J, Chonat S, Seu KG, Heeney MM, Zhang K, Hopkin RJ, Kalfa TA.Lesmana H, et al.Hum Mutat. 2018 Mar;39(3):389-393. doi: 10.1002/humu.23392. Epub 2018 Jan 11.Hum Mutat. 2018.PMID:29288557Free PMC article.
- Structural and Genetic Studies Demonstrate Neurologic Dysfunction in Triosephosphate Isomerase Deficiency Is Associated with Impaired Synaptic Vesicle Dynamics.Roland BP, Zeccola AM, Larsen SB, Amrich CG, Talsma AD, Stuchul KA, Heroux A, Levitan ES, VanDemark AP, Palladino MJ.Roland BP, et al.PLoS Genet. 2016 Mar 31;12(3):e1005941. doi: 10.1371/journal.pgen.1005941. eCollection 2016 Mar.PLoS Genet. 2016.PMID:27031109Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous