The need for biochemical testing in beta‐enolase deficiency in the genomic era
Abstract 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 pre...
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2019-11-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12070 |
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doaj-d63845f6ecd14928a17ec77c31c2009f2020-11-25T02:03:01ZengWileyJIMD Reports2192-83122019-11-01501404310.1002/jmd2.12070The need for biochemical testing in beta‐enolase deficiency in the genomic eraRalph Wigley0Renata S. Scalco1Alice R. Gardiner2Richard Godfrey3Suzanne Booth4Richard Kirk5David Hilton‐Jones6Henry Houlden7Simon Heales8Ros Quinlivan9Enzyme Laboratory, Department of Chemical Pathology, Cameilia Botnar Laboratories Great Ormond Street Hospital for Sick Children London UKMRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery London UKMRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery London UKMRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery London UKMRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery London UKSheffield Diagnostic Genetic Service Sheffield Children's NHS Foundation Trust Sheffield UKDepartment of Clinical Neurology West Wing, John Radcliffe Hospital Oxford UKMRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery London UKEnzyme Laboratory, Department of Chemical Pathology, Cameilia Botnar Laboratories Great Ormond Street Hospital for Sick Children London UKMRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery London UKAbstract 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 (Vmax). 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.https://doi.org/10.1002/jmd2.12070ENO3glycogen storage disease type XIIIkinetic profileβ‐enolase deficiency |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Ralph Wigley Renata S. Scalco Alice R. Gardiner Richard Godfrey Suzanne Booth Richard Kirk David Hilton‐Jones Henry Houlden Simon Heales Ros Quinlivan |
| spellingShingle |
Ralph Wigley Renata S. Scalco Alice R. Gardiner Richard Godfrey Suzanne Booth Richard Kirk David Hilton‐Jones Henry Houlden Simon Heales Ros Quinlivan The need for biochemical testing in beta‐enolase deficiency in the genomic era JIMD Reports ENO3 glycogen storage disease type XIII kinetic profile β‐enolase deficiency |
| author_facet |
Ralph Wigley Renata S. Scalco Alice R. Gardiner Richard Godfrey Suzanne Booth Richard Kirk David Hilton‐Jones Henry Houlden Simon Heales Ros Quinlivan |
| author_sort |
Ralph Wigley |
| title |
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_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_sort |
need for biochemical testing in beta‐enolase deficiency in the genomic era |
| publisher |
Wiley |
| series |
JIMD Reports |
| issn |
2192-8312 |
| publishDate |
2019-11-01 |
| description |
Abstract 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 (Vmax). 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. |
| topic |
ENO3 glycogen storage disease type XIII kinetic profile β‐enolase deficiency |
| url |
https://doi.org/10.1002/jmd2.12070 |
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