Clinical manifestations of mitochondria1 DNA depletion

Vu, Tuan; Sciacco, Monica; Tanji, Kurenai; Nichter, C.; Bonilla, Eduardo; Chatkupt, S.; Maertens, Paul; Shanske, Sara; Mendell, Jerry R.; Koenigsberger, M. Richard; Sharer, Leroy R.; Schon, Eric A.; DiMauro, Salvatore; DeVivo, Darryl C.

doi:10.1212/wnl.50.6.1783

Cited by 123 publications

(67 citation statements)

References 3 publications

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“…Of interest, there was less residual mtDNA in the liver of the more severely affected patient. Characteristically, children with mtDNA depletion have hyperCKemia, 16 which is also a feature of a few NNH patients (e.g., patient 1 in this report). Together, these findings suggest that depletion of mtDNA plays a pathogenetic role in NNH.…”

Section: Discussionmentioning

confidence: 51%

Navajo Neurohepatopathy: A Mitochondrial Dna Depletion Syndrome?

Tanji

Holve

et al. 2001

Hepatology

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Section: Discussionmentioning

confidence: 51%

Navajo Neurohepatopathy: A Mitochondrial Dna Depletion Syndrome?

Tanji

Holve

et al. 2001

Hepatology

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“…Typical symptoms include progressive external ophthalmoplegia (PEO), ptosis, and proximal weakness, but can also involve other systemic symptoms, including peripheral neuropathy, ataxia, dementia, sensorineural hearing loss, and other ocular symptoms. Many of these are adult onset in nature [48][49][50][51][52][53][54].…”

Section: Multiple Mtdna Deletion Disordersmentioning

confidence: 99%

“…These disorders were first described in 1991 [48], but have received tremendous attention since the discovery that mutations in POLG cause of one of the most devastating MDS disorders-Alpers-Huttenlocher syndrome (AHS). Infantile onset is common, with symptoms of epilepsy, hypotonia, developmental delay or regression, and hepatic failure that can be provoked by valproic acid [49]. Milder variants are associated with higher levels of mtDNA copy number, but can be slowly progressive and involve symptoms similar to the more severe phenotypes [50][51][52].…”

Section: Mitochondrial Dna Depletion Disordersmentioning

confidence: 99%

Mitochondrial Disease in Childhood: Nuclear Encoded

2013

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Primary mitochondrial disorders are clinically and genetically heterogeneous, caused by an alteration(s) in either mitochondrial DNA or nuclear DNA, and affect the respiratory chain's ability to undergo oxidative phosphorylation, leading to decreased production of adenosine triphosphophate and subsequent energy failure. These disorders may present at any age, but children tend to have an acute onset of disease compared with subacute or slowly progressive presentation in adults. Varying organ involvement also contributes to the phenotypic spectrum seen in these disorders. The childhood presentation of primary mitochondrial disease is mainly due to nuclear DNA mutations, with mitochondrial DNA mutations being less frequent in childhood and more prominent in adulthood disease. The clinician should be aware of the pediatric presentation of mitochondrial disease and have an understanding of the myriad of nuclear genes responsible for these disorders. The nuclear genes can be best understood by utilizing a classification system of location and function within the mitochondria.

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“…22 To our knowledge, mtDNA depletion has not been tested in neurodegenerative disorders, and specifically in AD, perhaps because up to now, the diagnosis of mtDNA depletion diseases has been based only on Southern blot analyses hybridising simultaneously with mtDNA and r18S probes. 17,22 ± 24 Such a technique requires a relatively high amount of DNA, is difficult to standardise and is susceptible to misinterpretations.…”

Section: Introductionmentioning

confidence: 99%

Is mitochondrial DNA depletion involved in Alzheimer's disease?

2001

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Several studies have suggested that mitochondrial metabolism disturbances and mitochondrial DNA (mtDNA) abnormalities may contribute to the progression of the pathology of Alzheimer's disease (AD). In this study we have investigated whether the amount of mtDNA is modified in different brain regions (cerebellum, hippocampus and frontal cortex) of confirmed AD necropsies and in blood of living AD patients. We used a real-time PCR method to analyse the mtDNA relative abundance in brain regions from 12 AD and seven controls and from a group of blood samples (17 living AD patients and 11 controls). MtDNA from blood samples together with hippocampus and cerebellum brain areas did not show differences between controls and AD. However, AD patients showed a 28% decrease in the amount of mtDNA in the frontal cortex when compared to controls for this specific area. Since frontal cortex is a severely affected region in AD, our results support the hypothesis that mitochondrial defects may play a role in the pathogenesis of AD. European Journal of Human Genetics (2001) 9, 279 ± 285.

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Clinical manifestations of mitochondria1 DNA depletion

Abstract: Inheritance appeared to be autosomal recessive, suggesting that mutations in nuclear DNA are responsible for mtDNA depletion. mtDNA depletion should be considered in children with mitochondrial disorders of uncertain etiology, and criteria for diagnosis are proposed.

Cited by 123 publications

References 3 publications

Navajo Neurohepatopathy: A Mitochondrial Dna Depletion Syndrome?

Navajo Neurohepatopathy: A Mitochondrial Dna Depletion Syndrome?

Mitochondrial Disease in Childhood: Nuclear Encoded

Is mitochondrial DNA depletion involved in Alzheimer's disease?

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