Primary CoQ
            <sub>10</sub>
            deficiency with a severe phenotype due to the c.901 C &gt; T (p.R301W) mutation in the COQ8A gene

Değerliyurt, Aydan; Gülleroğlu, Nadide Başak; Gül, Ayşe Esin Kibar

doi:10.1080/00207454.2022.2095269

Cited by 6 publications

(8 citation statements)

References 14 publications

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“…That same year, a 16-year-old girl presented to Degerliyut et al with recurrent seizures and ataxia [ 48 ]. Brain MRI revealed severe cerebellar atrophy, stroke-like lesions and a lactate peak on MR spectroscopy.…”

Section: Resultsmentioning

confidence: 99%

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Neuroimaging in Primary Coenzyme-Q10-Deficiency Disorders

et al. 2023

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Coenzyme Q10 (CoQ10) is an endogenously synthesized lipid molecule. It is best known for its role as a cofactor within the mitochondrial respiratory chain where it functions in electron transfer and ATP synthesis. However, there are many other cellular pathways that also depend on the CoQ10 supply (redox homeostasis, ferroptosis and sulfide oxidation). The CoQ10 biosynthesis pathway consists of several enzymes, which are encoded by the nuclear DNA. The majority of these enzymes are responsible for modifications of the CoQ-head group (benzoquinone ring). Only three enzymes (PDSS1, PDSS2 and COQ2) are required for assembly and attachment of the polyisoprenoid side chain. The head-modifying enzymes may assemble into resolvable domains, representing COQ complexes. During the last two decades, numerous inborn errors in CoQ10 biosynthesis enzymes have been identified. Thus far, 11 disease genes are known (PDSS1, PDSS2, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ8B, COQ9 and HPDL). Disease onset is highly variable and ranges from the neonatal period to late adulthood. CoQ10 deficiency exerts detrimental effects on the nervous system. Potential consequences are neuronal death, neuroinflammation and cerebral gliosis. Clinical features include encephalopathy, regression, movement disorders, epilepsy and intellectual disability. Brain magnetic resonance imaging (MRI) is the most important tool for diagnostic evaluation of neurological damage in individuals with CoQ10 deficiency. However, due to the rarity of the different gene defects, information on disease manifestations within the central nervous system is scarce. This review aims to provide an overview of brain MRI patterns observed in primary CoQ10 biosynthesis disorders and to highlight disease-specific findings.

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Section: Resultsmentioning

confidence: 99%

“…As mentioned above, stroke-like episodes were reported as a potential disease feature of several CoQ 10 biosynthesis defects (COQ2, COQ4 and COQ8A) [ 30 , 45 , 48 , 68 , 69 ]. Clinically, affected individuals may present with focal seizures, altered consciousness and hemiparesis.…”

Section: Discussionmentioning

confidence: 99%

Neuroimaging in Primary Coenzyme-Q10-Deficiency Disorders

et al. 2023

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“…The most common radiological finding in patients with CoQ8A is cerebellar atrophy that can be in different patterns (either localized, 4 diffused 27 , or pan-cerebellar 23 ). Other neuro-imaging radiological findings consist of cerebral and brainstem atrophy, stroke-like signal changes, infra-tentorial T2 hyperintensities, thin corpus callosum, enlarged ventricles, basal ganglia involvement, and thoraco-lumbar scoliosis.…”

Section: Discussionmentioning

confidence: 99%

Adolescence Onset Primary Coenzyme Q10 Deficiency With Rare CoQ8A Gene Mutation: A Case Report and Review of Literature

Hojabri

Gilani

Irilouzadian

et al. 2023

Clin Med Insights Case Rep

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Background: Primary deficiency of coenzyme Q10 deficiency-4 (CoQ10D4) is a heterogeneous disorder affecting different age groups. The main clinical manifestation consists of cerebellar ataxia, exercise intolerance, and dystonia. Case report: We provide a case of adolescence-onset ataxia, head tremor, and proximal muscle weakness accompanied by psychiatric features and abnormal serum urea (49.4 mg/dL), lactate (7.5 mmol/L), and CoQ10 level (0.4 µg/mL). Brain-MRI demonstrated cerebellar atrophy, thinning of the corpus callosum, and loss of white matter. Whole exome sequencing showed a homozygous missense mutation (c.911C>T; p.A304V) in CoQ8A gene which is a rare mutation and responsible variant of CoQ10D4. After supplementary treatment with CoQ10 50 mg/twice a day for 2 months the clinical symptoms improved. Conclusion: These observations highlight the significance of the early diagnosis of potentially treatable CoQ8A mutation as well as patient education and follow-up. Our findings widen the spectrum of CoQ8A phenotypic features so that clinicians be familiar with the disease not only in severe childhood-onset ataxia but also in adolescence with accompanying psychiatric problems.

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“…Paprocka et al [ 84 ] described a 22-month-old girl with cerebellar ataxia and developmental regression resulting from a COQ8A mutation ([c.811C>T] [p.Arg271Cys] who showed improved communication and growth following supplementation with CoQ10 (300 mg/day for 3 months). Degerliyurt et al [ 85 ] reported on a 16-year-old patient with ataxia, cerebellar atrophy, and cardiomyopathy resulting from a COQ8A mutation ([c901 C>T] [p. Arg301Trp]); the authors noted that supplementation with CoQ10 was started at too late a stage in disease to prevent the death of the patient. The most comprehensive study on patients with COQ8A mutations was carried out by Traschutz et al [ 86 ], who assessed 64 patients (including 39 previously unreported) from 51 families across 16 different countries.…”

Section: Clinical Studies Relating To Coq Gene Mutationsmentioning

confidence: 99%

Primary Coenzyme Q10 Deficiency: An Update

Mantle,

Millichap,

Castro-Marrero

et al. 2023

Antioxidants

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Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant and plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Due to the multiplicity of roles in cell function, it is not surprising that a deficiency in CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation; we have attempted to resolve the disparities between previous review articles regarding the usefulness or otherwise of CoQ10 supplementation in these disorders. In addition, we have highlighted several of the potential problems relating to CoQ10 supplementation in primary CoQ10 deficiency, as well as identifying unresolved issues relating to these disorders that require further research.

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Primary CoQ ₁₀ deficiency with a severe phenotype due to the c.901 C > T (p.R301W) mutation in the COQ8A gene

Cited by 6 publications

References 14 publications

Neuroimaging in Primary Coenzyme-Q10-Deficiency Disorders

Neuroimaging in Primary Coenzyme-Q10-Deficiency Disorders

Adolescence Onset Primary Coenzyme Q10 Deficiency With Rare CoQ8A Gene Mutation: A Case Report and Review of Literature

Primary Coenzyme Q10 Deficiency: An Update

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Primary CoQ 10 deficiency with a severe phenotype due to the c.901 C > T (p.R301W) mutation in the COQ8A gene

Cited by 6 publications

References 14 publications

Neuroimaging in Primary Coenzyme-Q10-Deficiency Disorders

Neuroimaging in Primary Coenzyme-Q10-Deficiency Disorders

Adolescence Onset Primary Coenzyme Q10 Deficiency With Rare CoQ8A Gene Mutation: A Case Report and Review of Literature

Primary Coenzyme Q10 Deficiency: An Update

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Primary CoQ ₁₀ deficiency with a severe phenotype due to the c.901 C > T (p.R301W) mutation in the COQ8A gene