Infantile and pediatric quinone deficiency diseases

Rötig, Agnès; Mollet, Julie; Rio, Marlène; Münnich, Arnold

doi:10.1016/j.mito.2007.02.008

Cited by 59 publications

(58 citation statements)

References 25 publications

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“…Coenzyme Q (CoQ) shuttles electrons from complex I and complex II to complex III. 13 The hypothesis of a deficiency in quinone-dependent complexes was strengthened by the restoration of complex II þ III activity after incubation with exogenous ubiquinone, but we found no mutation in genes known to be involved in the CoQ 10 biosynthesis pathway. At this stage, we were unable to determine whether this deficiency in CI þ CIII and CII þ CIII was related to a primary defect in the biosynthesis pathway of CoQ 10 or a secondary problem to another etiology.…”

Section: Discussionmentioning

confidence: 58%

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Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

et al. 2012

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We report two children, born from consanguineous parents, who presented with early-onset refractory epilepsy associated with psychomotor delay, failure to thrive, blindness and deafness. Polarographic and spectrophotometric analyses in fibroblasts and liver revealed a respiratory chain (RC) dysfunction. Surprisingly, we identified a homozygous nonsense mutation in the GM3 synthase gene by using exome sequencing. GM3 synthase catalyzes the formation of GM3 ganglioside from lactosylceramide, which is the first step in the synthesis of complex ganglioside species. Mass spectrometry analysis revealed that the complete absence of GM3 ganglioside and its biosynthetic derivatives was associated with an upregulation of the alternative globoside pathway in fibroblasts. The accumulation of Gb3 and Gb4 globosides likely has a role in RC dysfunction and in the decrease of mitochondrial membrane potential leading to apoptosis, which we observed in fibroblasts. We show for the first time that GM3 synthase deficiency, responsible for early-onset epilepsy syndrome, leads to a secondary RC dysfunction. Our study highlights the role of secondary mitochondrial disorders that can interfere with the diagnosis and the evolution of other metabolic diseases.

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Section: Discussionmentioning

confidence: 58%

“…12 Microsatellite DNA markers flanking 17 genes involved in the CoQ 10 biosynthesis pathway were analyzed. 13 In the two affected children, we found homozygosity at the PDSS2 (NM_020381) and ADCK4 (NM_001142555) loci. Direct sequencing of these two genes revealed no mutation.…”

Section: Molecular Analysismentioning

confidence: 76%

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

et al. 2012

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“…Primary deficiency of coenzyme Q10 (CoQ10) is a genetically heterogeneous disorder, with a highly variable clinical spectrum, which includes multi-systemic manifestations as well as CNS compromise [14][15][16] . Five clinical subtypes have been recognized: (1) Encephalomyophatic, with mitochondrial myopathy, recurrent myoglobinuria and CNS symptoms and signs; (2) Early infantile multisystemic, with severe visceral and brain manifestations; (3) Leigh syndrome; (4) Pure myopathic; (5) Ataxic 14,15,17 .…”

Section: Ataxia With Coenzyme Q10 Deficiencymentioning

confidence: 99%

“…Five clinical subtypes have been recognized: (1) Encephalomyophatic, with mitochondrial myopathy, recurrent myoglobinuria and CNS symptoms and signs; (2) Early infantile multisystemic, with severe visceral and brain manifestations; (3) Leigh syndrome; (4) Pure myopathic; (5) Ataxic 14,15,17 .…”

Section: Ataxia With Coenzyme Q10 Deficiencymentioning

confidence: 99%

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Autosomal recessive ataxias: 20 types, and counting

Embiruçu

Martyn

Schlesinger

et al. 2009

Arq. Neuro-Psiquiatr.

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-More than 140 years after the first description of Friedreich ataxia, autosomal recessive ataxias have become one of the more complex fields in Neurogenetics. Currently this group of diseases contains more than 20 clinical entities and an even larger number of associated genes. Some disorders are very rare, restricted to isolated populations, and others are found worldwide. An expressive number of recessive ataxias are treatable, and responsibility for an accurate diagnosis is high. The purpose of this review is to update the practitioner on clinical and pathophysiological aspects of these disorders and to present an algorithm to guide the diagnosis.KEY WORDS: autosomal recessive ataxias, cerebellar ataxia, cerebellum, Friedreich ataxia.Ataxias autossômicas recessivas: 20 tipos e muito mais resumo -Mais de 140 anos após a primeira descrição da ataxia de Friedreich, as ataxias autossômicas recessivas se transformaram em um dos mais complexos campos da Neurogenética. Atualmente, este grupo de doenças é composto por mais de 20 entidades clínicas e possui um número ainda maior de genes associados. Algumas doenças são muito raras, tendo sido observadas apenas em populações isoladas, enquanto que outras são encontradas no mundo todo. Um número expressivo de ataxias é tratável, e a responsabilidade em se fazer um diagnóstico correto é alta. A finalidade desta revisão é a de atualizar o neurologista a respeito dos principais aspectos clínicos e fisiopatológicos destas doenças e de apresentar um algoritmo para auxiliar a sua investigação e o seu diagnóstico.

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A fatal case of COQ7‐associated primary coenzyme Q₁₀ deficiency

et al. 2019

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Background Primary coenzyme Q 10 (CoQ 10 ) deficiencies are clinically and genetically heterogeneous group of disorders associated with defects of genes involved in the CoQ 10 biosynthesis pathway. COQ7 ‐associated CoQ 10 deficiency is very rare and only two cases have been reported. Methods and Results We report a patient with encephalo‐myo‐nephro‐cardiopathy, persistent lactic acidosis, and basal ganglia lesions resulting in early infantile death. Using whole exome sequencing, we identified compound heterozygous variants in the COQ7 gene consisting of a deletion insertion resulting in frameshift [c.599_600delinsTAATGCATC, p.(Lys200Ilefs*56)] and a missense substitution [c.319C>T, p.(Arg107Trp), NM_016138.4]. Skin fibroblast studies showed decreased combined complex II + III activity and reduction in CoQ 10 level. Conclusion This third patient presenting with lethal encephalo‐myo‐nephro‐cardiopathy represents the severe end of this ultra‐rare mitochondrial disease caused by biallelic COQ7 mutations. The response to CoQ 10 supplement is poor and alternative treatment strategies should be developed for a more effective management of this disorder.

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Infantile and pediatric quinone deficiency diseases

Cited by 59 publications

References 25 publications

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

Autosomal recessive ataxias: 20 types, and counting

A fatal case of COQ7‐associated primary coenzyme Q₁₀ deficiency

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Infantile and pediatric quinone deficiency diseases

Cited by 59 publications

References 25 publications

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

Autosomal recessive ataxias: 20 types, and counting

A fatal case of COQ7‐associated primary coenzyme Q10 deficiency

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A fatal case of COQ7‐associated primary coenzyme Q₁₀ deficiency