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The dilemma of diagnosing coenzyme Q10 deficiency in muscle.
Mol Genet Metab. 2018 09; 125(1-2):38-43.MG

Abstract

BACKGROUND

Coenzyme Q10 (CoQ10) is an important component of the mitochondrial respiratory chain (RC) and is critical for energy production. Although the prevalence of CoQ10 deficiency is still unknown, the general consensus is that the condition is under-diagnosed. The aim of this study was to retrospectively investigate CoQ10 deficiency in frozen muscle specimens in a cohort of ethnically diverse patients who received muscle biopsies for the investigation of a possible RC deficiency (RCD).

METHODS

Muscle samples were homogenized whereby 600 ×g supernatants were used to analyze RC enzyme activities, followed by quantification of CoQ10 by stable isotope dilution liquid chromatography tandem mass spectrometry. The experimental group consisted of 156 patients of which 76 had enzymatically confirmed RCDs. To further assist in the diagnosis of CoQ10 deficiency in this cohort, we included sequencing of 18 selected nuclear genes involved with CoQ10 biogenesis in 26 patients with low CoQ10 concentration in muscle samples.

RESULTS

Central 95% reference intervals (RI) were established for CoQ10 normalized to citrate synthase (CS) or protein. Nine patients were considered CoQ10 deficient when expressed against CS, while 12 were considered deficient when expressed against protein. In two of these patients the molecular genetic cause could be confirmed, of which one would not have been identified as CoQ10 deficient if expressed only against protein content.

CONCLUSION

In this retrospective study, we report a central 95% reference interval for 600 ×g muscle supernatants prepared from frozen samples. The study reiterates the importance of including CoQ10 quantification as part of a diagnostic approach to study mitochondrial disease as it may complement respiratory chain enzyme assays with the possible identification of patients that may benefit from CoQ10 supplementation. However, the anomaly that only a few patients were identified as CoQ10 deficient against both markers (CS and protein), while the majority of patients where only CoQ10 deficient against one of the markers (and not the other), remains problematic. We therefore conclude from our data that, to prevent possibly not diagnosing a potential CoQ10 deficiency, the expression of CoQ10 levels in muscle on both CS as well as protein content should be considered.

Authors+Show Affiliations

Human Metabolomics, North-West University (Potchefstroom Campus), Potchefstroom, South Africa. Electronic address: Roan.Louw@nwu.ac.za.Department of Paediatrics and Child Health, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa.Human Metabolomics, North-West University (Potchefstroom Campus), Potchefstroom, South Africa.Human Metabolomics, North-West University (Potchefstroom Campus), Potchefstroom, South Africa.Human Metabolomics, North-West University (Potchefstroom Campus), Potchefstroom, South Africa.Human Metabolomics, North-West University (Potchefstroom Campus), Potchefstroom, South Africa.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29530532

Citation

Louw, Roan, et al. "The Dilemma of Diagnosing Coenzyme Q10 Deficiency in Muscle." Molecular Genetics and Metabolism, vol. 125, no. 1-2, 2018, pp. 38-43.
Louw R, Smuts I, Wilsenach KL, et al. The dilemma of diagnosing coenzyme Q10 deficiency in muscle. Mol Genet Metab. 2018;125(1-2):38-43.
Louw, R., Smuts, I., Wilsenach, K. L., Jonck, L. M., Schoonen, M., & van der Westhuizen, F. H. (2018). The dilemma of diagnosing coenzyme Q10 deficiency in muscle. Molecular Genetics and Metabolism, 125(1-2), 38-43. https://doi.org/10.1016/j.ymgme.2018.02.015
Louw R, et al. The Dilemma of Diagnosing Coenzyme Q10 Deficiency in Muscle. Mol Genet Metab. 2018;125(1-2):38-43. PubMed PMID: 29530532.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The dilemma of diagnosing coenzyme Q10 deficiency in muscle. AU - Louw,Roan, AU - Smuts,Izelle, AU - Wilsenach,Kimmey-Li, AU - Jonck,Lindi-Maryn, AU - Schoonen,Maryke, AU - van der Westhuizen,Francois H, Y1 - 2018/02/23/ PY - 2017/12/19/received PY - 2018/02/21/revised PY - 2018/02/21/accepted PY - 2018/3/14/pubmed PY - 2019/4/27/medline PY - 2018/3/14/entrez KW - Coenzyme Q10 deficiency KW - Complex II+III KW - Electron transport chain KW - OXPHOS KW - Reference range SP - 38 EP - 43 JF - Molecular genetics and metabolism JO - Mol Genet Metab VL - 125 IS - 1-2 N2 - BACKGROUND: Coenzyme Q10 (CoQ10) is an important component of the mitochondrial respiratory chain (RC) and is critical for energy production. Although the prevalence of CoQ10 deficiency is still unknown, the general consensus is that the condition is under-diagnosed. The aim of this study was to retrospectively investigate CoQ10 deficiency in frozen muscle specimens in a cohort of ethnically diverse patients who received muscle biopsies for the investigation of a possible RC deficiency (RCD). METHODS: Muscle samples were homogenized whereby 600 ×g supernatants were used to analyze RC enzyme activities, followed by quantification of CoQ10 by stable isotope dilution liquid chromatography tandem mass spectrometry. The experimental group consisted of 156 patients of which 76 had enzymatically confirmed RCDs. To further assist in the diagnosis of CoQ10 deficiency in this cohort, we included sequencing of 18 selected nuclear genes involved with CoQ10 biogenesis in 26 patients with low CoQ10 concentration in muscle samples. RESULTS: Central 95% reference intervals (RI) were established for CoQ10 normalized to citrate synthase (CS) or protein. Nine patients were considered CoQ10 deficient when expressed against CS, while 12 were considered deficient when expressed against protein. In two of these patients the molecular genetic cause could be confirmed, of which one would not have been identified as CoQ10 deficient if expressed only against protein content. CONCLUSION: In this retrospective study, we report a central 95% reference interval for 600 ×g muscle supernatants prepared from frozen samples. The study reiterates the importance of including CoQ10 quantification as part of a diagnostic approach to study mitochondrial disease as it may complement respiratory chain enzyme assays with the possible identification of patients that may benefit from CoQ10 supplementation. However, the anomaly that only a few patients were identified as CoQ10 deficient against both markers (CS and protein), while the majority of patients where only CoQ10 deficient against one of the markers (and not the other), remains problematic. We therefore conclude from our data that, to prevent possibly not diagnosing a potential CoQ10 deficiency, the expression of CoQ10 levels in muscle on both CS as well as protein content should be considered. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/29530532/The_dilemma_of_diagnosing_coenzyme_Q10_deficiency_in_muscle_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(17)31227-1 DB - PRIME DP - Unbound Medicine ER -