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The need for biochemical testing in beta‐enolase deficiency in the genomic era

Glycogen storage disease type XIII (GSDXIII) is a very rare inherited metabolic myopathy characterized by autosomal‐recessive mutations in the ENO3 gene resulting in muscle β‐enolase deficiency, an enzymatic defect of the distal part of glycolysis. Enzyme kinetic studies of two patients presenting w...

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Autores principales: Wigley, Ralph, Scalco, Renata S., Gardiner, Alice R., Godfrey, Richard, Booth, Suzanne, Kirk, Richard, Hilton‐Jones, David, Houlden, Henry, Heales, Simon, Quinlivan, Ros
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851005/
https://www.ncbi.nlm.nih.gov/pubmed/31741825
http://dx.doi.org/10.1002/jmd2.12070
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author Wigley, Ralph
Scalco, Renata S.
Gardiner, Alice R.
Godfrey, Richard
Booth, Suzanne
Kirk, Richard
Hilton‐Jones, David
Houlden, Henry
Heales, Simon
Quinlivan, Ros
author_facet Wigley, Ralph
Scalco, Renata S.
Gardiner, Alice R.
Godfrey, Richard
Booth, Suzanne
Kirk, Richard
Hilton‐Jones, David
Houlden, Henry
Heales, Simon
Quinlivan, Ros
author_sort Wigley, Ralph
collection PubMed
description Glycogen storage disease type XIII (GSDXIII) is a very rare inherited metabolic myopathy characterized by autosomal‐recessive mutations in the ENO3 gene resulting in muscle β‐enolase deficiency, an enzymatic defect of the distal part of glycolysis. Enzyme kinetic studies of two patients presenting with exertion intolerance and recurrent rhabdomyolysis are reported. Next generation sequencing confirmed patient 1 was homozygous for p.E187K in ENO3, while patient 2 was homozygous for p.C357Y. ENO3 variants pathogenicity was confirmed by functional studies in skeletal muscle. p.E187K caused extremely low total enolase activity. p.C357Y was associated with a higher level of residual activity but kinetic studies showed a lower maximum work rate (V (max)). This study illustrates that GSDXIII may be caused by either null mutations leading to β‐enolase deficiency or by mutations that alter the enzyme's kinetic profile. This study highlights the importance of carrying out functional studies as part of the diagnostic process following the identification of variants with next generation sequencing.
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spelling pubmed-68510052019-11-18 The need for biochemical testing in beta‐enolase deficiency in the genomic era Wigley, Ralph Scalco, Renata S. Gardiner, Alice R. Godfrey, Richard Booth, Suzanne Kirk, Richard Hilton‐Jones, David Houlden, Henry Heales, Simon Quinlivan, Ros JIMD Rep Research Reports Glycogen storage disease type XIII (GSDXIII) is a very rare inherited metabolic myopathy characterized by autosomal‐recessive mutations in the ENO3 gene resulting in muscle β‐enolase deficiency, an enzymatic defect of the distal part of glycolysis. Enzyme kinetic studies of two patients presenting with exertion intolerance and recurrent rhabdomyolysis are reported. Next generation sequencing confirmed patient 1 was homozygous for p.E187K in ENO3, while patient 2 was homozygous for p.C357Y. ENO3 variants pathogenicity was confirmed by functional studies in skeletal muscle. p.E187K caused extremely low total enolase activity. p.C357Y was associated with a higher level of residual activity but kinetic studies showed a lower maximum work rate (V (max)). This study illustrates that GSDXIII may be caused by either null mutations leading to β‐enolase deficiency or by mutations that alter the enzyme's kinetic profile. This study highlights the importance of carrying out functional studies as part of the diagnostic process following the identification of variants with next generation sequencing. John Wiley & Sons, Inc. 2019-09-03 /pmc/articles/PMC6851005/ /pubmed/31741825 http://dx.doi.org/10.1002/jmd2.12070 Text en © 2019 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Reports
Wigley, Ralph
Scalco, Renata S.
Gardiner, Alice R.
Godfrey, Richard
Booth, Suzanne
Kirk, Richard
Hilton‐Jones, David
Houlden, Henry
Heales, Simon
Quinlivan, Ros
The need for biochemical testing in beta‐enolase deficiency in the genomic era
title The need for biochemical testing in beta‐enolase deficiency in the genomic era
title_full The need for biochemical testing in beta‐enolase deficiency in the genomic era
title_fullStr The need for biochemical testing in beta‐enolase deficiency in the genomic era
title_full_unstemmed The need for biochemical testing in beta‐enolase deficiency in the genomic era
title_short The need for biochemical testing in beta‐enolase deficiency in the genomic era
title_sort need for biochemical testing in beta‐enolase deficiency in the genomic era
topic Research Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851005/
https://www.ncbi.nlm.nih.gov/pubmed/31741825
http://dx.doi.org/10.1002/jmd2.12070
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