Serum Creatine Kinase and Transaminase Levels in Duchenne and Becker Muscular Dystrophies
Corresponding Author
Marie Rohlenová
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Correspondence:
Marie Rohlenová ([email protected])
Contribution: Conceptualization, Investigation, Funding acquisition, Writing - original draft, Methodology, Visualization, Project administration
Search for more papers by this authorKateřina Machová
UAM Czech Republic s.r.o, Prague, Czech Republic
Contribution: Methodology, Formal analysis, Visualization
Search for more papers by this authorJana Baranová
Institute of Biostatistics and Analyses, s.r.o, Brno, Czech Republic
Contribution: Data curation, Formal analysis, Methodology, Writing - review & editing, Visualization
Search for more papers by this authorLenka Mokrá
Institute of Biostatistics and Analyses, s.r.o, Brno, Czech Republic
Contribution: Methodology, Formal analysis, Data curation, Writing - review & editing, Visualization
Search for more papers by this authorLivie Mensová
Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorRadim Mazanec
Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Supervision, Writing - review & editing
Search for more papers by this authorLenka Juříková
Department of Children's Neurology, University Hospital Brno, And Faculty of Medicine Masaryk University in Brno, Brno, Czech Republic
Contribution: Writing - review & editing, Investigation
Search for more papers by this authorJan Staněk
Department of Pediatric Neurology, Faculty Hospital Ostrava, Ostrava, Czech Republic
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorPetra Fuchsová
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Writing - review & editing, Investigation
Search for more papers by this authorBarbora Lauerová
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Investigation, Writing - review & editing, Resources
Search for more papers by this authorMarkéta Kumhera
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Writing - review & editing, Investigation
Search for more papers by this authorJana Haberlová
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Conceptualization, Investigation, Supervision, Writing - review & editing, Validation, Resources, Funding acquisition
Search for more papers by this authorCorresponding Author
Marie Rohlenová
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Correspondence:
Marie Rohlenová ([email protected])
Contribution: Conceptualization, Investigation, Funding acquisition, Writing - original draft, Methodology, Visualization, Project administration
Search for more papers by this authorKateřina Machová
UAM Czech Republic s.r.o, Prague, Czech Republic
Contribution: Methodology, Formal analysis, Visualization
Search for more papers by this authorJana Baranová
Institute of Biostatistics and Analyses, s.r.o, Brno, Czech Republic
Contribution: Data curation, Formal analysis, Methodology, Writing - review & editing, Visualization
Search for more papers by this authorLenka Mokrá
Institute of Biostatistics and Analyses, s.r.o, Brno, Czech Republic
Contribution: Methodology, Formal analysis, Data curation, Writing - review & editing, Visualization
Search for more papers by this authorLivie Mensová
Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorRadim Mazanec
Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Supervision, Writing - review & editing
Search for more papers by this authorLenka Juříková
Department of Children's Neurology, University Hospital Brno, And Faculty of Medicine Masaryk University in Brno, Brno, Czech Republic
Contribution: Writing - review & editing, Investigation
Search for more papers by this authorJan Staněk
Department of Pediatric Neurology, Faculty Hospital Ostrava, Ostrava, Czech Republic
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorPetra Fuchsová
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Writing - review & editing, Investigation
Search for more papers by this authorBarbora Lauerová
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Investigation, Writing - review & editing, Resources
Search for more papers by this authorMarkéta Kumhera
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Writing - review & editing, Investigation
Search for more papers by this authorJana Haberlová
Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Contribution: Conceptualization, Investigation, Supervision, Writing - review & editing, Validation, Resources, Funding acquisition
Search for more papers by this authorFunding: This work was supported by European Reference Network for Neuromuscular Disieases; Czech Ministry of Health, the project for conceptual development of research organization Nr. 00064203; Grantová Agentura, Univerzita Karlova, 586120.
A part of the material was presented as a poster Nr. 348: Liver or Muscle—CK/Transaminase Ratio in a Cohort of Patients with Muscular Dystrophy, on the 16th International Congress of Neuromuscular Diseases (ICNMD 2021), virtual. (Neuromuscular diseases: 16th International Congress on Neuromuscular Diseases, 21–22 and 28–29 May 2021 Virtual, Worldwide. J Neuromuscul Dis. 2021;8(s1):S1–S171. doi: 10.3233/JND-219006. PMID: 34334417).
ABSTRACT
Introduction/Aims
The distinction between hepatic and muscular origin of transaminases in Duchenne (DMD) and Becker (BMD) muscular dystrophy is challenging. We aimed to describe the relations between creatine kinase (CK), lactate dehydrogenase (LDH), myoglobin, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), and their evolution with age, the severity of the disease, and its complications (corticosteroid therapy, cardiac ejection fraction, body mass index [BMI]).
Methods
Multiple regression analysis of the studied markers was performed in three cohorts: 1. Retrospective data of 212 DMD and BMD boys available in the national registry of muscular dystrophies (REaDY), and 2. Cross-sectional study supplemented by retrospective data of A. 64 DMD boys and B. 18 adults with either BMD or B/DMD carriers.
Results
The estimation of normal levels of transaminases from CK levels was: ALT [UI/L] = 228.508 + 0.011*CK [UI/L] ± 341.822for DMD, and ALT [UI/L] = 124.498 + 0.011*CK [UI/L] ± 341.822for BMD. AST [UI/L] = 167.436 + 0.012*CK [UI/L]–6.323*Age ± 249.804 for both (all p < 0.001). In the smaller cohort, ALT was best predicted by LDH and physical performance, whereas AST was defined by CK and LDH combined (all p < 0.001). In DMD, all AST, ALT, CK, LDH, and myoglobin decreased with age (p < 0.001), while GGT increased with age and BMI (both p < 0.001).
Discussion
Transaminases are dependent on CK and LDH in dystrophinopathy. There is an increase in GGT in DMD connected to BMI.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Supporting Information
| Filename | Description |
|---|---|
| mus28431-sup-0001-FigureS1.pdfPDF document, 303.1 KB |
Figure S1. Repeated measures of CK, LDH, Myoglobin, ALT, AST, and GGT in each individual patients, as available, and their evolvement with age. |
| mus28431-sup-0002-FigureS2.pdfPDF document, 156.6 KB |
Figure S2. Local data of a sinlge neuromuscular center. The dependence of the traditional hepatic markers (on y axes), in their respective rows, on the traditional muscular markers (on x axes) in their respective collumns: ALT [ukat/l] (first row), AST [ukat/l] (second row) and GGT [ukat/l] (third row) on CK [ukat/l] (first column), Myoglobin [ug/l] (second column) and LDH [ukat/l] (third column) in DMD (blue dots) and BMD/Carriers (orange dots) Cohorts from the single NM center. In the graph, we also provided the values in IU/l, and mmol/l for myoglobin (orange triangles for the BMD/Carriers cohort, and blue hexagons for the DMD Cohort)—those are shown on the minor axes (up and in the right in each graph). The equations of linear regression are added to each graph for both the international (lower equation) and SI units (upper equation). Note that for those equations comparing all parameters in ukat/l (converted to IU/l), the slope of the curve is the same. For myoglobin, there is a different integer due to the difference between the conversion factors. p value counted by linear regression is provided for each relationship, with those lower than 0.05 in bold. |
| mus28431-sup-0003-TableS1.docxWord 2007 document , 16.1 KB |
Table S1. Normal values of the analyzed enzymes. |
| mus28431-sup-0004-TableS2.docxWord 2007 document , 12.7 KB |
Table S2. Dependence of ALT and AST parameters on the values of the CK parameter at the enrollment and site of patient—all sites (Hospitals A, B, and C) (N = 212). |
| mus28431-sup-0005-TableS3.docxWord 2007 document , 16 KB |
Table S3. The dependance of the studied markers (CK, LDH, Myoglobin, ALT, AST, GGT) on age. The table shows the coefficients of linear regression for ukat(l (first column)), and UI/l (second column), and the p value for the linear dependence of each studied marker on age. |
| mus28431-sup-0006-TableS4.docxWord 2007 document , 18.9 KB |
Table S4. The dependance of ALT, AST, and GGT on age, levels of myoglobin, CK, LDH, ambulatory status and NSAA in ambulatory patients. Only statistically significant variables are included in the final model. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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