McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients
A clinical, biochemical, histological and molecular genetic analysis of 60 McArdle patients (33 males and 27 females; mean age at diagnosis: 37 years) was performed. The objective of this study was to identify a possible genotype−phenotype correlation in McArdle disease. All patients compl...
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| Format: | Article |
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MDPI AG
2020-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/2/33 |
| _version_ | 1818028117934997504 |
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| author | Pushpa Raj Joshi Marcus Deschauer Stephan Zierz |
| author_facet | Pushpa Raj Joshi Marcus Deschauer Stephan Zierz |
| author_sort | Pushpa Raj Joshi |
| collection | DOAJ |
| description | A clinical, biochemical, histological and molecular genetic analysis of 60 McArdle patients (33 males and 27 females; mean age at diagnosis: 37 years) was performed. The objective of this study was to identify a possible genotype−phenotype correlation in McArdle disease. All patients complained of exercise-induced myalgia and fatigue; permanent weakness was present in 47% of the patients. Five percent of patients conveyed of masticatory muscle weakness. Age of onset was <15 years in 92% patients. Serum creatine kinase was elevated 5 to13-fold. Forearm ischemic test showed decreased lactate production but excessively increased ammonia upon exercise (<i>n</i> = 16). Muscle biopsies revealed highly reduced or missing myophosphorylase activity (<i>n</i> = 20) (mean: 0.17 ± 0.35 U/g tissue; normal: 12−61) and histologically, sub-sarcolemmal glycogen accumulation (<i>n</i> = 9). Molecular genetic analysis revealed the common p.Arg50Ter mutation in 68% of the patients. Other rather frequent mutations were p.Arg270Ter (allele frequency: 5%) followed by c.2262delA and p.Met1Val (allele frequencies: 3%). Twenty-four other rare mutations were also identified. No genotype−phenotype correlation was observed. The analysis highlights that testing of the p.Arg50Ter mutation could be performed first in molecular genetic testing of patients with exercise intolerance possibly due to McArdle disease. However, there is enormous mutation heterogeneity in McArdle disease thus sequencing of the myophosphorylase gene is needed in patients highly suspicious of McArdle disease. |
| first_indexed | 2024-12-10T04:58:42Z |
| format | Article |
| id | doaj.art-c31706fd2db04bcfadd1a17f55393a90 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-12-10T04:58:42Z |
| publishDate | 2020-02-01 |
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| spelling | doaj.art-c31706fd2db04bcfadd1a17f55393a902022-12-22T02:01:27ZengMDPI AGBiomedicines2227-90592020-02-01823310.3390/biomedicines8020033biomedicines8020033McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 PatientsPushpa Raj Joshi0Marcus Deschauer1Stephan Zierz2Department of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), GermanyDepartment of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), GermanyDepartment of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), GermanyA clinical, biochemical, histological and molecular genetic analysis of 60 McArdle patients (33 males and 27 females; mean age at diagnosis: 37 years) was performed. The objective of this study was to identify a possible genotype−phenotype correlation in McArdle disease. All patients complained of exercise-induced myalgia and fatigue; permanent weakness was present in 47% of the patients. Five percent of patients conveyed of masticatory muscle weakness. Age of onset was <15 years in 92% patients. Serum creatine kinase was elevated 5 to13-fold. Forearm ischemic test showed decreased lactate production but excessively increased ammonia upon exercise (<i>n</i> = 16). Muscle biopsies revealed highly reduced or missing myophosphorylase activity (<i>n</i> = 20) (mean: 0.17 ± 0.35 U/g tissue; normal: 12−61) and histologically, sub-sarcolemmal glycogen accumulation (<i>n</i> = 9). Molecular genetic analysis revealed the common p.Arg50Ter mutation in 68% of the patients. Other rather frequent mutations were p.Arg270Ter (allele frequency: 5%) followed by c.2262delA and p.Met1Val (allele frequencies: 3%). Twenty-four other rare mutations were also identified. No genotype−phenotype correlation was observed. The analysis highlights that testing of the p.Arg50Ter mutation could be performed first in molecular genetic testing of patients with exercise intolerance possibly due to McArdle disease. However, there is enormous mutation heterogeneity in McArdle disease thus sequencing of the myophosphorylase gene is needed in patients highly suspicious of McArdle disease.https://www.mdpi.com/2227-9059/8/2/33mcardlesecond-windmyophosphorylasemutationpermanent weakness |
| spellingShingle | Pushpa Raj Joshi Marcus Deschauer Stephan Zierz McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients Biomedicines mcardle second-wind myophosphorylase mutation permanent weakness |
| title | McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients |
| title_full | McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients |
| title_fullStr | McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients |
| title_full_unstemmed | McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients |
| title_short | McArdle Disease: Clinical, Biochemical, Histological and Molecular Genetic Analysis of 60 Patients |
| title_sort | mcardle disease clinical biochemical histological and molecular genetic analysis of 60 patients |
| topic | mcardle second-wind myophosphorylase mutation permanent weakness |
| url | https://www.mdpi.com/2227-9059/8/2/33 |
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