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Michio Hirano - One of the best experts on this subject based on the ideXlab platform.

  • the coq2 genotype predicts the severity of Coenzyme Q10 Deficiency
    Human Molecular Genetics, 2016
    Co-Authors: Maria Andrea Desbats, Michio Hirano, Mara Doimo, Matteo Cassina, Valeria Morbidoni, Micol Silicbenussi, Vincenzo Ciminale, Sabrina Sacconi, Giuseppe Asso, Fabie Pierrel
    Abstract:

    COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10 (CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ Deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-onset encephalopathy. However, the reasons of this variability are still unknown.We have characterized the structure of human COQ2, defined its subcellular localization and developed a yeast model to validate all the mutant alleles reported so far.Our findings show that the main functional transcript of COQ2 is shorter than what was previously reported and that its protein product localizes to mitochondria with the C-terminus facing the intermembrane space. Complementation experiments in yeast showed that the residual activity of the mutant proteins correlates with the clinical phenotypes observed in patients.We defined the structure of COQ2 with relevant implications for mutation screening in patients and demonstrated that, contrary to other COQ gene defects such as ADCK3, there is a correlation between COQ2 genotype and patient's phenotype.

  • Clinical presentations of Coenzyme Q10 Deficiency syndrome.
    Molecular syndromology, 2014
    Co-Authors: Catarina M Quinzii, Valentina Emmanuele, Michio Hirano
    Abstract:

    Coenzyme Q10 (CoQ10) Deficiency is a clinically and genetically heterogeneous syndrome which has been associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) nephropathy, (4) cerebellar ataxia, and (5) isolated myopathy. Of these phenotypes, cerebellar ataxia and syndromic or isolated nephrotic syndrome are the most common. CoQ10 Deficiency predominantly presents in childhood. To date, causative mutations have been identified in a small proportion of patients, making it difficult to identify a phenotype-genotype correlation. Identification of CoQ10 Deficiency is important because the disease, in particular muscle symptoms and nephropathy, frequently responds to CoQ10 supplementation.

  • Coenzyme Q10 Deficiency and Cerebellar Ataxia
    2014
    Co-Authors: Lorenzo Peverelli, Ali Naini, Michio Hirano, Catarina M
    Abstract:

    Coenzyme Q10 (CoQ10) Deficiency is an autosomal recessive disorder presenting five main phenotypes: an enchephalomyopathic form, a severe infantile neurological syndrome, a nephrotic form, a pure myopathic form and an ataxic form. The last one, the focus of this review, is the most common phenotype, characterized by childhood/ young adulthood-onset cerebellar ataxia and cerebellar atrophy as main neurological signs, and decreased CoQ10 levels in muscle (the hallmark of the disease), and sometimes in fibroblasts. Molecular defects have been described in two different genes: APTX and ADCK3. Early diagnosis is important because patients can benefit from CoQ10 supplementation.

  • heterogeneity of Coenzyme Q10 Deficiency patient study and literature review
    JAMA Neurology, 2012
    Co-Authors: Valentina Emmanuele, Ali Naini, Salvatore Dimauro, Catarina M Quinzii, Luis C Lopez, Andres Berardo, Saba Tadesse, Erin Dagostino, Martha Solomon, Michio Hirano
    Abstract:

    Coenzyme Q 10 (CoQ 10 ) Deficiency has been associated with 5 major clinical phenotypes: encephalomyopathy, severe infantile multisystemic disease, nephropathy, cerebellar ataxia, and isolated myopathy. Primary CoQ 10 Deficiency is due to defects in CoQ 10 biosynthesis, while secondary forms are due to other causes. A review of 149 cases, including our cohort of 76 patients, confirms that CoQ 10 Deficiency is a clinically and genetically heterogeneous syndrome that mainly begins in childhood and predominantly manifests as cerebellar ataxia. Coenzyme Q 10 measurement in muscle is the gold standard for diagnosis. Identification of CoQ 10 Deficiency is important because the condition frequently responds to treatment. Causative mutations have been identified in a small proportion of patients.

  • 176th enmc international workshop diagnosis and treatment of Coenzyme Q10 Deficiency
    Neuromuscular Disorders, 2012
    Co-Authors: Shamima Rahma, Catherine F Clarke, Michio Hirano
    Abstract:

    An ENMC meeting was held in Naarden, the Netherlands (July 9–11th 2010) with 12 clinical and basic scientists and 3 industrial representatives from Europe (France, Belgium, Germany, Italy, Spain, Switzerland, the Netherlands and the UK) and the USA, to discuss their collective experience with the molecular underpinnings, diagnosis, and management of patients with Deficiency of Coenzyme Q10 (CoQ10). CoQ10, also known as ubiquinone, is a unique electron carrier [1]. It is essential for aerobic organisms because of its role in mitochondrial energy production as a chaperone of electrons from complexes I and II (and also from the electron transfer flavoproteins, ETF) to complex III of the respiratory chain. In addition, this lipophilic molecule has numerous other vital functions in cells that include: serving as antioxidant in both lipoproteins and cell membranes; connecting energy production with important cellular pathways such as the cell cycle and DNA replication and repair through its role in pyrimidine biosynthesis; modulation of apoptosis through its regulation of the transition pore; and maintenance of body temperature via its action on uncoupling proteins. The aims of this workshop were: to define how to clinically recognise and diagnose patients with CoQ10 Deficiency; to optimize strategies to identify the underlying molecular genetic defects; to review basic CoQ10 biology; and to delineate therapeutic options for this group of disorders, which represent the most readily treatable subset of mitochondrial diseases.

Rafael Artuch - One of the best experts on this subject based on the ideXlab platform.

  • laboratory diagnosis of a case with Coenzyme Q10 Deficiency
    Clinical Chemistry, 2020
    Co-Authors: Abraham J Paredesfuentes, Carlos Santosocana, Raquel Montero, Delia Yubero, Natalia Juliapalacios, Maria Victoria Cascajoalmenara, Angels Garciacazorla, Rafael Artuch
    Abstract:

    This work was supported by grants from the Instituto de Salud Carlos III (ISCIII-FIS PI17/00109 and PI17/01286). A.J. Paredes-Fuentes, a grant from the Instituto de Salud Carlos III (FI18/00253).

  • Molecular diagnosis of Coenzyme Q10 Deficiency: an update
    Expert review of molecular diagnostics, 2018
    Co-Authors: Delia Yubero, Plácido Navas, Leonardo Salviati, Raquel Montero, Carlos Santos-ocaña, Rafael Artuch
    Abstract:

    ABSTRACTIntroduction: Coenzyme Q10 (CoQ) Deficiency syndromes comprise a growing number of genetic disorders. While primary CoQ Deficiency syndromes are rare diseases, secondary deficiencies have b...

  • Molecular diagnosis of Coenzyme Q10 Deficiency.
    Expert review of molecular diagnostics, 2015
    Co-Authors: Delia Yubero, Plácido Navas, Leonardo Salviati, Raquel Montero, Judith Armstrong, Carmen Espinós, Francesc Palau, Carlos Santos-ocaña, Rafael Artuch
    Abstract:

    Coenzyme Q10 (CoQ) Deficiency syndromes comprise a growing number of neurological and extraneurological disorders. Primary-genetic but also secondary CoQ deficiencies have been reported. The biochemical determination of CoQ is a good tool for the rapid identification of CoQ deficiencies but does not allow the selection of candidate genes for molecular diagnosis. Moreover, the metabolic pathway for CoQ synthesis is an intricate and not well-understood process, where a large number of genes are implicated. Thus, only next-generation sequencing techniques (either genetic panels of whole-exome and -genome sequencing) are at present appropriate for a rapid and realistic molecular diagnosis of these syndromes. The potential treatability of CoQ Deficiency strongly supports the necessity of a rapid molecular characterization of patients, since primary CoQ deficiencies may respond well to CoQ treatment.

  • Biochemical diagnosis of Coenzyme Q10 Deficiency.
    Molecular syndromology, 2014
    Co-Authors: Delia Yubero, Raquel Montero, John M. Land, Rafael Artuch, Simon J. R. Heales, Iain P Hargreaves
    Abstract:

    Coenzyme Q10 (CoQ10) Deficiency appears to have a particularly heterogeneous clinical presentation. However, there appear to be 5 recognisable clinical phenotypes: encephalomyopathy, severe infantile multisystemic disease, nephropathy, cerebellar ataxia, and isolated myopathy. However, although useful, clinical symptoms alone are insufficient for the definitive diagnosis of CoQ10 Deficiency which relies upon biochemical assessment of tissue CoQ10 status. In this article, we review the biochemical methods used in the diagnosis of human CoQ10 Deficiency and indicate the most appropriate tissues for this evaluation.

  • Coenzyme Q10 Deficiency in mitochondrial DNA depletion syndromes
    Mitochondrion, 2013
    Co-Authors: Raquel Montero, Aleix Navarro-sastre, Ester López-gallardo, Julio Montoya, Iain P Hargreaves, Manuela Grazina, Paz Briones, John M. Land, Rafael Artuch, M. O'callaghan
    Abstract:

    Abstract We evaluated Coenzyme Q10 (CoQ) levels in patients studied under suspicion of mitochondrial DNA depletion syndromes (MDS) (n = 39). CoQ levels were quantified by HPLC, and the percentage of mtDNA depletion by quantitative real-time PCR. A high percentage of MDS patients presented with CoQ Deficiency as compared to other mitochondrial patients (Mann–Whitney-U test: p = 0.001). Our findings suggest that MDS are frequently associated with CoQ Deficiency, as a possible secondary consequence of disease pathophysiology. Assessment of muscle CoQ status seems advisable in MDS patients since the possibility of CoQ supplementation may then be considered as a candidate therapy.

Catarina M Quinzii - One of the best experts on this subject based on the ideXlab platform.

  • Primary Coenzyme Q10 Deficiency-7: expanded phenotypic spectrum and a founder mutation in southern Chinese
    NPJ genomic medicine, 2019
    Co-Authors: Mandy H. Y. Tsang, Sophie Hon Yu Lai, Donald M.l. Tse, Brooke R. Willis, Anna Ka Yee Kwong, Yen Yin Chou, Shuan-pei Lin, Catarina M Quinzii
    Abstract:

    Primary Coenzyme Q10 Deficiency-7 (COQ10D7) is a rare mitochondrial disease caused by biallelic mutations in COQ4. Here we report the largest cohort of COQ10D7 to date, with 11 southern Chinese patients confirmed with biallelic COQ4 mutations. Five of them have the classical neonatal-onset encephalo-cardiomyopathy, while the others have infantile onset with more heterogeneous clinical presentations. We also identify a founder mutation COQ4 (NM_016035.5): c.370G>A, p.(Gly124Ser) for COQ10D7, suggesting a higher chance of occurrence in the southern Chinese. This study helps improve understanding of the clinical spectrum of this disorder.

  • The clinical heterogeneity of Coenzyme Q10 Deficiency results from genotypic differences in the Coq9 gene
    EMBO molecular medicine, 2015
    Co-Authors: Marta Luna-sánchez, Catarina M Quinzii, Emanuele Barca, Elena Díaz-casado, Miguel Á. Tejada, Ángeles Montilla-garcía, Enrique Javier Cobos, Germaine Escames, Darío Acuña-castroviejo, Luis C Lopez
    Abstract:

    Primary Coenzyme Q10 (CoQ10) Deficiency is due to mutations in genes involved in CoQ biosynthesis. The disease has been associated with five major phenotypes, but a genotype–phenotype correlation is unclear. Here, we compare two mouse models with a genetic modification in Coq9 gene (Coq9 Q95X and Coq9 R239X ), and their responses to 2,4-dihydroxybenzoic acid (2,4-diHB). Coq9 R239X mice manifest severe widespread CoQ Deficiency associated with fatal encephalomyopathy and respond to 2,4-diHB increasing CoQ levels. In contrast, Coq9 Q95X mice exhibit mild CoQ Deficiency manifesting with reduction in CI+III activity and mitochondrial respiration in skeletal muscle, and late-onset mild mitochondrial myopathy, which does not respond to 2,4-diHB. We show that these differences are due to the levels of COQ biosynthetic proteins, suggesting that the presence of a truncated version of COQ9 protein in Coq9 R239X mice destabilizes the CoQ multiprotein complex. Our study points out the importance of the multiprotein complex for CoQ biosynthesis in mammals, which may provide new insights to understand the genotype– phenotype heterogeneity associated with human CoQ Deficiency and may have a potential impact on the treatment of this mitochondrial disorder.

  • Clinical presentations of Coenzyme Q10 Deficiency syndrome.
    Molecular syndromology, 2014
    Co-Authors: Catarina M Quinzii, Valentina Emmanuele, Michio Hirano
    Abstract:

    Coenzyme Q10 (CoQ10) Deficiency is a clinically and genetically heterogeneous syndrome which has been associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) nephropathy, (4) cerebellar ataxia, and (5) isolated myopathy. Of these phenotypes, cerebellar ataxia and syndromic or isolated nephrotic syndrome are the most common. CoQ10 Deficiency predominantly presents in childhood. To date, causative mutations have been identified in a small proportion of patients, making it difficult to identify a phenotype-genotype correlation. Identification of CoQ10 Deficiency is important because the disease, in particular muscle symptoms and nephropathy, frequently responds to CoQ10 supplementation.

  • heterogeneity of Coenzyme Q10 Deficiency patient study and literature review
    JAMA Neurology, 2012
    Co-Authors: Valentina Emmanuele, Ali Naini, Salvatore Dimauro, Catarina M Quinzii, Luis C Lopez, Andres Berardo, Saba Tadesse, Erin Dagostino, Martha Solomon, Michio Hirano
    Abstract:

    Coenzyme Q 10 (CoQ 10 ) Deficiency has been associated with 5 major clinical phenotypes: encephalomyopathy, severe infantile multisystemic disease, nephropathy, cerebellar ataxia, and isolated myopathy. Primary CoQ 10 Deficiency is due to defects in CoQ 10 biosynthesis, while secondary forms are due to other causes. A review of 149 cases, including our cohort of 76 patients, confirms that CoQ 10 Deficiency is a clinically and genetically heterogeneous syndrome that mainly begins in childhood and predominantly manifests as cerebellar ataxia. Coenzyme Q 10 measurement in muscle is the gold standard for diagnosis. Identification of CoQ 10 Deficiency is important because the condition frequently responds to treatment. Causative mutations have been identified in a small proportion of patients.

  • a nonsense mutation in coq9 causes autosomal recessive neonatal onset primary Coenzyme Q10 Deficiency a potentially treatable form of mitochondrial disease
    American Journal of Human Genetics, 2009
    Co-Authors: Andrew J Duncan, Michio Hirano, Catarina M Quinzii, Maria Bitnerglindzicz, Brigitte Meunier, Harry Costello, Luis C Lopez, Michael I Sadowski, Iain P Hargreaves, John Hardy
    Abstract:

    Coenzyme Q10 is a mobile lipophilic electron carrier located in the inner mitochondrial membrane. Defects of Coenzyme Q10 biosynthesis represent one of the few treatable mitochondrial diseases. We genotyped a patient with primary Coenzyme Q10 Deficiency who presented with neonatal lactic acidosis and later developed multisytem disease including intractable seizures, global developmental delay, hypertrophic cardiomyopathy, and renal tubular dysfunction. Cultured skin fibroblasts from the patient had a Coenzyme Q10 biosynthetic rate of 11% of normal controls and accumulated an abnormal metabolite that we believe to be a biosynthetic intermediate. In view of the rarity of Coenzyme Q10 Deficiency, we hypothesized that the disease-causing gene might lie in a region of ancestral homozygosity by descent. Data from an Illumina HumanHap550 array were analyzed with BeadStudio software. Sixteen regions of homozygosity >1.5 Mb were identified in the affected infant. Two of these regions included the loci of two of 16 candidate genes implicated in human Coenzyme Q10 biosynthesis. Sequence analysis demonstrated a homozygous stop mutation affecting a highly conserved residue of COQ9, leading to the truncation of 75 amino acids. Site-directed mutagenesis targeting the equivalent residue in the yeast Saccharomyces cerevisiae abolished respiratory growth.

Leonardo Salviati - One of the best experts on this subject based on the ideXlab platform.

  • Molecular diagnosis of Coenzyme Q10 Deficiency: an update
    Expert review of molecular diagnostics, 2018
    Co-Authors: Delia Yubero, Plácido Navas, Leonardo Salviati, Raquel Montero, Carlos Santos-ocaña, Rafael Artuch
    Abstract:

    ABSTRACTIntroduction: Coenzyme Q10 (CoQ) Deficiency syndromes comprise a growing number of genetic disorders. While primary CoQ Deficiency syndromes are rare diseases, secondary deficiencies have b...

  • Molecular diagnosis of Coenzyme Q10 Deficiency.
    Expert review of molecular diagnostics, 2015
    Co-Authors: Delia Yubero, Plácido Navas, Leonardo Salviati, Raquel Montero, Judith Armstrong, Carmen Espinós, Francesc Palau, Carlos Santos-ocaña, Rafael Artuch
    Abstract:

    Coenzyme Q10 (CoQ) Deficiency syndromes comprise a growing number of neurological and extraneurological disorders. Primary-genetic but also secondary CoQ deficiencies have been reported. The biochemical determination of CoQ is a good tool for the rapid identification of CoQ deficiencies but does not allow the selection of candidate genes for molecular diagnosis. Moreover, the metabolic pathway for CoQ synthesis is an intricate and not well-understood process, where a large number of genes are implicated. Thus, only next-generation sequencing techniques (either genetic panels of whole-exome and -genome sequencing) are at present appropriate for a rapid and realistic molecular diagnosis of these syndromes. The potential treatability of CoQ Deficiency strongly supports the necessity of a rapid molecular characterization of patients, since primary CoQ deficiencies may respond well to CoQ treatment.

  • genetics of Coenzyme Q10 Deficiency
    Molecular Syndromology, 2014
    Co-Authors: Mara Doimo, Maria Andrea Desbats, Cristina Cerqua, Matteo Cassina, Eva Trevisso, Leonardo Salviati
    Abstract:

    Coenzyme Q10 (CoQ10) is an essential component of eukaryotic cells and is involved in crucial biochemical reactions such as the production of ATP in the mitochondrial respiratory chain, the biosynthesis of pyrimidines, and the modulation of apoptosis. CoQ10 requires at least 13 genes for its biosynthesis. Mutations in these genes cause primary CoQ10 Deficiency, a clinically and genetically heterogeneous disorder. To date mutations in 8 genes (PDSS1, PDSS2, COQ2, COQ4, COQ6, ADCK3, ADCK4, and COQ9) have been associated with CoQ10 Deficiency presenting with a wide variety of clinical manifestations. Onset can be at virtually any age, although pediatric forms are more common. Symptoms include those typical of respiratory chain disorders (encephalomyopathy, ataxia, lactic acidosis, deafness, retinitis pigmentosa, hypertrophic cardiomyopathy), but some (such as steroid-resistant nephrotic syndrome) are peculiar to this condition. The molecular bases of the clinical diversity of this condition are still unknown. It is of critical importance that physicians promptly recognize these disorders because most patients respond to oral administration of CoQ10.

  • effect of vanillic acid on coq6 mutants identified in patients with Coenzyme Q10 Deficiency
    Biochimica et Biophysica Acta, 2014
    Co-Authors: Mara Doimo, Plácido Navas, Eva Trevisso, Fabie Pierrel, Ranna Airik, Marc Ergdoll, Carlos Santosocana, Friedhelm Hildebrand, Leonardo Salviati
    Abstract:

    Human COQ6 encodes a monooxygenase which is responsible for the C5-hydroxylation of the quinone ring of Coenzyme Q (CoQ). Mutations in COQ6 cause primary CoQ Deficiency, a condition responsive to oral CoQ10 supplementation. Treatment is however still problematic given the poor bioavailability of CoQ10. We employed S. cerevisiae lacking the orthologous gene to characterize the two different human COQ6 isoforms and the mutations found in patients. COQ6 isoform a can partially complement the defective yeast, while isoform b, which lacks part of the FAD-binding domain, is inactive but partially stable, and could have a regulatory/inhibitory function in CoQ10 biosynthesis. Most mutations identified in patients, including the frameshift Q461fs478X mutation, retain residual enzymatic activity, and all patients carry at least one hypomorphic allele, confirming that the complete block of CoQ biosynthesis is lethal. These mutants are also partially stable and allow the assembly of the CoQ biosynthetic complex. In fact treatment with two hydroxylated analogues of 4-hydroxybenzoic acid, namely, vanillic acid or 3-4-hydroxybenzoic acid, restored the respiratory growth of yeast Δcoq6 cells expressing the mutant huCOQ6-isoa proteins. These compounds, and particularly vanillic acid, could therefore represent an interesting therapeutic option for COQ6 patients.

  • haploinsufficiency of coq4 causes Coenzyme Q10 Deficiency
    Journal of Medical Genetics, 2012
    Co-Authors: Leonardo Salviati, Mara Doimo, Maria Andrea Desbats, Matteo Cassina, Eva Trevisso, Maria Angeles Rodriguez Hernandez, Alberto Casari, Vanessa Pertegato, Caterina Agosto, Geppo Sartori
    Abstract:

    Background COQ4 encodes a protein that organises the multienzyme complex for the synthesis of Coenzyme Q10 (CoQ10). A 3.9 Mb deletion of chromosome 9q34.13 was identified in a 3-year-old boy with mental retardation, encephalomyopathy and dysmorphic features. Because the deletion encompassed COQ4, the patient was screened for CoQ10 Deficiency. Methods A complete molecular and biochemical characterisation of the patient's fibroblasts and of a yeast model were performed. Results The study found reduced COQ4 expression (48% of controls), CoQ10 content and biosynthetic rate (44% and 43% of controls), and activities of respiratory chain complex II+III. Cells displayed a growth defect that was corrected by the addition of CoQ10 to the culture medium. Knockdown of COQ4 in HeLa cells also resulted in a reduction of CoQ10. Diploid yeast haploinsufficient for COQ4 displayed similar CoQ Deficiency. Haploinsufficency of other genes involved in CoQ10 biosynthesis does not cause CoQ Deficiency, underscoring the critical role of COQ4 . Oral CoQ10 supplementation resulted in a significant improvement of neuromuscular symptoms, which reappeared after supplementation was temporarily discontinued. Conclusion Mutations of COQ4 should be searched for in patients with CoQ10 Deficiency and encephalomyopathy; patients with genomic rearrangements involving COQ4 should be screened for CoQ10 Deficiency, as they could benefit from supplementation.

Alan Pestronk - One of the best experts on this subject based on the ideXlab platform.

  • Coenzyme Q10 Deficiency in children frequent type 2c muscle fibers with normal morphology
    Muscle & Nerve, 2013
    Co-Authors: Brian R Sommerville, Craig M. Zaidman, Alan Pestronk
    Abstract:

    Introduction: Neurological disorders with low tissue Coenzyme Q10 (CoQ10) levels are important to identify, as they may be treatable. Methods: We evaluated retrospectively clinical, laboratory, and muscle histochemistry and oxidative enzyme characteristics in 49 children with suspected mitochondrial disorders. We compared 18 with CoQ10 Deficiency in muscle to 31 with normal CoQ10 values. Results: Muscle from CoQ10-deficient patients averaged 5.5-fold more frequent type 2C muscle fibers than controls (P < 0.0001). A type 2C fiber frequency of ≥ 5% had 89% sensitivity and 84% specificity for CoQ10 Deficiency in this cohort. No biopsy showed active myopathy. There were no differences between groups in frequencies of mitochondrial myopathologic, clinical, or laboratory features. Multiple abnormalities in muscle oxidative enzyme activities were more frequent in CoQ10-deficient patients than in controls. Conclusions: When a childhood mitochondrial disorder is suspected, an increased frequency of type 2C fibers in morphologically normal muscle suggests CoQ10 Deficiency. Muscle Nerve 48:722–726, 2013

  • Coenzyme Q10 Deficiency in children: frequent type 2C muscle fibers with normal morphology.
    Muscle & nerve, 2013
    Co-Authors: R. Brian Sommerville, Craig M. Zaidman, Alan Pestronk
    Abstract:

    Introduction: Neurological disorders with low tissue Coenzyme Q10 (CoQ10) levels are important to identify, as they may be treatable. Methods: We evaluated retrospectively clinical, laboratory, and muscle histochemistry and oxidative enzyme characteristics in 49 children with suspected mitochondrial disorders. We compared 18 with CoQ10 Deficiency in muscle to 31 with normal CoQ10 values. Results: Muscle from CoQ10-deficient patients averaged 5.5-fold more frequent type 2C muscle fibers than controls (P