Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: A CoQ10-responsive condition

Salviati, Leonardo; Sacconi, Sabrina; Murer, Luisa; Zacchello, G; Franceschini, Lorenzo; Laverda, Anna Maria; Basso, Giuseppe; Quinzii, Catarina M.; Angelini, C.; Hirano, Michio; Naini, Ali; Navas, Plácido; DiMauro, Salvatore; Montini, Giovanni

doi:10.1212/01.wnl.0000172859.55579.a7

Cited by 177 publications

(149 citation statements)

References 9 publications

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“…The peculiarity of CoQ10 deficiency among mitochondrial disorders is that patients respond well to oral supplementation with CoQ10, making this the only currently treatable mitochondrial disorder. High-dose oral CoQ10 supplementation can stop the progression of the encephalopathy (23) and also of the renal manifestations in patients with COQ2 (24), COQ6 (25) and ADCK4 (16) mutations. However, oral CoQ10 supplementation showed no response on heart function in our elder sister, maybe because it was too late for her disease course.…”

Section: Resultsmentioning

confidence: 99%

Steroid-resistant nephrotic syndrome caused by co-inheritance of mutations at NPHS1 and ADCK4 genes in two Chinese siblings

Zhang

Wang

Liu

et al. 2017

IRDR

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Section: Resultsmentioning

confidence: 99%

Steroid-resistant nephrotic syndrome caused by co-inheritance of mutations at NPHS1 and ADCK4 genes in two Chinese siblings

Zhang

Wang

Liu

et al. 2017

IRDR

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“…Treatment with exogenous CoQ 10 has successfully slowed disease progression of some cases of human CoQ deficiency (25,26). To verify that CoQ deficiency was the cause of the degenerative phenotype in C. elegans, we incubated coq-1 RNAi-treated animals with CoQ 10 .…”

Section: Resultsmentioning

confidence: 99%

Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration

Earls

Hacker²,

Watson³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria are key regulators of cell viability and provide essential functions that protect against neurodegenerative disease. To develop a model for mitochondrial-dependent neurodegeneration in Caenorhabditis elegans, we used RNA interference (RNAi) and genetic ablation to knock down expression of enzymes in the Coenzyme Q (CoQ) biosynthetic pathway. CoQ is a required component of the ATP-producing electron transport chain in mitochondria. We found that reduced levels of CoQ result in a progressive uncoordinated (Unc) phenotype that is correlated with the appearance of degenerating GABA neurons. Both the Unc and degenerative phenotypes emerge during late larval development and progress in adults. Neuron classes in motor and sensory circuits that use other neurotransmitters (dopamine, acetylcholine, glutamate, serotonin) and body muscle cells were less sensitive to CoQ depletion. Our results indicate that the mechanism of GABA neuron degeneration is calcium-dependent and requires activation of the apoptotic gene, ced-4 (Apaf-1). A molecular cascade involving mitochondrial-initiated cell death is also consistent with our finding that GABA neuron degeneration requires the mitochondrial fission gene, drp-1. We conclude that the cell selectivity and developmental progression of CoQ deficiency in C. elegans indicate that this model may be useful for delineating the role of mitochondrial dysfunction in neurodegenerative disease.cell death | disease | mitochondria | neurodegeneration | necrosis

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“…Table 2 lists the major extrarenal manifestations associated with gene defects causing syndromic SRNS; if extra-renal manifestations are present, it is highly likely that a causative mutation will be identified. A full description of syndromic SRNS is beyond the scope of this review but readers are directed to several detailed reviews for a thorough discussion [5,20,21,44,45,50,55,84,86,87].…”

Section: Syndromic Srns and Mitochondrial Disordersmentioning

confidence: 99%

Genetic testing in steroid-resistant nephrotic syndrome: why, who, when and how?

2017

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Steroid-resistant nephrotic syndrome (SRNS) is a common cause of chronic kidney disease in childhood and has a significant risk of rapid progression to end-stage renal disease. The identification of over 50 monogenic causes of SRNS has revealed dysfunction in podocyte-associated proteins in the pathogenesis of proteinuria, highlighting their essential role in glomerular function. Recent technological advances in high-throughput sequencing have enabled indication-driven genetic panel testing for patients with SRNS. The availability of genetic testing, combined with the significant phenotypic variability of monogenic SRNS, poses unique challenges for clinicians when directing genetic testing. This highlights the need for clear clinical guidelines that provide a systematic approach for mutational screening in SRNS. The likelihood of identifying a causative mutation is inversely related to age at disease onset and is increased with a positive family history or the presence of extra-renal manifestations. An unequivocal molecular diagnosis could allow for a personalised treatment approach with weaning of immunosuppressive therapy, avoidance of renal biopsy and provision of accurate, well-informed genetic counselling. Identification of novel causative mutations will continue to unravel the pathogenic mechanisms of glomerular disease and provide new insights into podocyte biology and glomerular function.

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Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: A CoQ10-responsive condition

Cited by 177 publications

References 9 publications

Steroid-resistant nephrotic syndrome caused by co-inheritance of mutations at <i>NPHS1</i> and <i>ADCK4</i> genes in two Chinese siblings

Steroid-resistant nephrotic syndrome caused by co-inheritance of mutations at <i>NPHS1</i> and <i>ADCK4</i> genes in two Chinese siblings

Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration

Genetic testing in steroid-resistant nephrotic syndrome: why, who, when and how?

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