Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes
Abstract Background Pyruvate dehydrogenase complex (PDHC) deficiency is a common neurodegenerative disease associated with abnormal mitochondrial energy metabolism. The diagnosis of PDHC is difficult because of the lack of a rapid, accurate, and cost‐effective clinical diagnostic method. Methods A 4...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1728 |
| _version_ | 1819064731588100096 |
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| author | YanYan Ma YaoGang Zhang Tao Zhang Zhu Man XiaoMing Su ShuJing Hao TianZe Wang |
| author_facet | YanYan Ma YaoGang Zhang Tao Zhang Zhu Man XiaoMing Su ShuJing Hao TianZe Wang |
| author_sort | YanYan Ma |
| collection | DOAJ |
| description | Abstract Background Pyruvate dehydrogenase complex (PDHC) deficiency is a common neurodegenerative disease associated with abnormal mitochondrial energy metabolism. The diagnosis of PDHC is difficult because of the lack of a rapid, accurate, and cost‐effective clinical diagnostic method. Methods A 4‐year‐old boy was preliminarily diagnosed with putative Leigh syndrome based on the clinical presentation. PDHC activity in peripheral blood leukocytes and a corresponding gene analysis were subsequently undertaken. Sodium pyruvate 1‐13C was used for the analysis of PDHC activity in peripheral leukocytes. The genes encoding PDHC were then scanned for mutations. Results The results showed that the corresponding PDHC activity was dramatically decreased to 10.5 nmol/h/mg protein as compared with that of healthy controls (124.6 ± 7.1 nmol/h/mg). The ratio of PDHC to citrate synthase was 2.1% (control: 425.3 ± 27.1). The mutation analysis led to the identification of a missense mutation, NM_000284.4:g214C>T, in exon 3 of PDHC. Conclusion The peripheral blood leukocyte PDHC activity assay may provide a practical enzymatic diagnostic method for PDHC‐related mitochondrial diseases. |
| first_indexed | 2024-12-21T15:35:14Z |
| format | Article |
| id | doaj.art-501024e40b354ffda53b227b8a8795bf |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-12-21T15:35:14Z |
| publishDate | 2021-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-501024e40b354ffda53b227b8a8795bf2022-12-21T18:58:39ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-08-0198n/an/a10.1002/mgg3.1728Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytesYanYan Ma0YaoGang Zhang1Tao Zhang2Zhu Man3XiaoMing Su4ShuJing Hao5TianZe Wang6Central Laboratory of Qinghai University Affiliated Hospital Xining ChinaCentral Laboratory of Qinghai University Affiliated Hospital Xining ChinaNeurological Department of Qinghai University Affiliated Hospital Xining ChinaNeurological Department of Qinghai University Affiliated Hospital Xining ChinaNeurological Department of Qinghai University Affiliated Hospital Xining ChinaChinovoLaboratory Beijing P. R. ChinaChinovoLaboratory Beijing P. R. ChinaAbstract Background Pyruvate dehydrogenase complex (PDHC) deficiency is a common neurodegenerative disease associated with abnormal mitochondrial energy metabolism. The diagnosis of PDHC is difficult because of the lack of a rapid, accurate, and cost‐effective clinical diagnostic method. Methods A 4‐year‐old boy was preliminarily diagnosed with putative Leigh syndrome based on the clinical presentation. PDHC activity in peripheral blood leukocytes and a corresponding gene analysis were subsequently undertaken. Sodium pyruvate 1‐13C was used for the analysis of PDHC activity in peripheral leukocytes. The genes encoding PDHC were then scanned for mutations. Results The results showed that the corresponding PDHC activity was dramatically decreased to 10.5 nmol/h/mg protein as compared with that of healthy controls (124.6 ± 7.1 nmol/h/mg). The ratio of PDHC to citrate synthase was 2.1% (control: 425.3 ± 27.1). The mutation analysis led to the identification of a missense mutation, NM_000284.4:g214C>T, in exon 3 of PDHC. Conclusion The peripheral blood leukocyte PDHC activity assay may provide a practical enzymatic diagnostic method for PDHC‐related mitochondrial diseases.https://doi.org/10.1002/mgg3.1728Leigh syndromeleukocytePDHA1pyruvate dehydrogenase complex (PDHC) |
| spellingShingle | YanYan Ma YaoGang Zhang Tao Zhang Zhu Man XiaoMing Su ShuJing Hao TianZe Wang Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes Molecular Genetics & Genomic Medicine Leigh syndrome leukocyte PDHA1 pyruvate dehydrogenase complex (PDHC) |
| title | Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes |
| title_full | Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes |
| title_fullStr | Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes |
| title_full_unstemmed | Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes |
| title_short | Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes |
| title_sort | pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes |
| topic | Leigh syndrome leukocyte PDHA1 pyruvate dehydrogenase complex (PDHC) |
| url | https://doi.org/10.1002/mgg3.1728 |
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