Infectious stress triggers a POLG-related mitochondrial disease

Gaudó, Paula; Emperador, Sonia; Garrido-Pérez, Nuria; Ruiz‐Pesini, Eduardo; Yubero, Dèlia; García‐Cazorla, Àngels; Artuch, Rafael; Montoya, Julio; Bayona‐Bafaluy, M. Pilar

doi:10.1007/s10048-019-00593-2

Cited by 15 publications

(23 citation statements)

References 48 publications

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“…The initial search from combined databases returned 228 articles (PubMed = 118 and Embase = 110). A total of 48, including 195 cases, met the inclusion criteria and were used for further evaluation [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ].…”

Section: Resultsmentioning

confidence: 99%

POLG1-Related Epilepsy: Review of Diagnostic and Therapeutic Findings

et al. 2020

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Background: The clinical spectrum associated with POLG1 gene mutations ranges from non-syndromic epilepsy or mild isolated neurological signs to neurodegenerative disorders. Our aim was to review diagnostic findings, therapeutic approaches and outcomes of reported cases of epilepsy related to POLG1 mutation. Methods: The articles for review were identified through a systematic research on PubMed and EMBASE databases from January 2003 to April 2020, searching for the terms “Epilepsy AND POLG OR polymerase gamma,” OR “POLG1”. Results: Forty-eight articles were selected for review, which included 195 patients. Two main peaks of age at epilepsy onset were found: at ages 1 and 13 years. The most frequent seizure type was myoclonic. The occurrence of Status Epilepticus was reported in 46.4% of cases. Epileptiform and slow abnormalities were most frequently seen over occipital regions. Brain Magnetic Resonance Imaging (MRI) revealed increased T2 signal intensities in thalamic regions. Genetic analysis revealed a prevalence of A467T, W748S and G848S (74.2% of patients) mutations. Survival at 5 years was estimated at very low levels (30.2% of patients). Conclusion: In this review, we included cases with both pediatric and adult epilepsy onset. The analysis of data regarding prognosis showed that survival is related to age at onset of epilepsy.

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Section: Resultsmentioning

confidence: 99%

POLG1-Related Epilepsy: Review of Diagnostic and Therapeutic Findings

et al. 2020

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“…Clinical and scientific literature link mitochondrial diseases with a higher susceptibility to infection, in particular respiratory and enterobacterial infection ( McKee et al., 2000 ), and with an increased risk of crises and disease progression ( Morgan-Hughes, 1986 ; Edmonds, 2004 ; Varghese et al., 2011 ; Al-Zubeidi et al., 2014 ; Gaudó et al., 2020 ). Strikingly, disease progression is not reverted after the pathogen has been cleared ( Edmonds et al., 2002 ).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial respiration restricts Listeria monocytogenes infection by slowing down host cell receptor recycling

et al. 2021

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“…While a robust link has not yet been established, viral infection and fever have been reported to coincide with symptom onset in mitochondrial disease [21,[90][91][92][93][94][95]. For example, in three unrelated patients with POLG mutations, symptom onset followed infection with human herpesvirus 6 or Borrelia [96,97]. These patients all presented with severe seizures and rapid progressive neurodegeneration despite antivirals and antibiotics treatment and were eventually diagnosed with mitochondrial disease caused by POLG.…”

Section: Immunologic Stress As a Possible Catalyst For Symptomsmentioning

confidence: 99%

The immune system as a driver of mitochondrial disease pathogenesis: a review of evidence

Hanaford

Johnson

2022

Orphanet J Rare Dis

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Background Genetic mitochondrial diseases represent a significant challenge to human health. These diseases are extraordinarily heterogeneous in clinical presentation and genetic origin, and often involve multi-system disease with severe progressive symptoms. Mitochondrial diseases represent the most common cause of inherited metabolic disorders and one of the most common causes of inherited neurologic diseases, yet no proven therapeutic strategies yet exist. The basic cell and molecular mechanisms underlying the pathogenesis of mitochondrial diseases have not been resolved, hampering efforts to develop therapeutic agents. Main body In recent pre-clinical work, we have shown that pharmacologic agents targeting the immune system can prevent disease in the Ndufs4(KO) model of Leigh syndrome, indicating that the immune system plays a causal role in the pathogenesis of at least this form of mitochondrial disease. Intriguingly, a number of case reports have indicated that immune-targeting therapeutics may be beneficial in the setting of genetic mitochondrial disease. Here, we summarize clinical and pre-clinical evidence suggesting a key role for the immune system in mediating the pathogenesis of at least some forms of genetic mitochondrial disease. Conclusions Significant clinical and pre-clinical evidence indicates a key role for the immune system as a significant in the pathogenesis of at least some forms of genetic mitochondrial disease.

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Infectious stress triggers a POLG-related mitochondrial disease

Cited by 15 publications

References 48 publications

POLG1-Related Epilepsy: Review of Diagnostic and Therapeutic Findings

POLG1-Related Epilepsy: Review of Diagnostic and Therapeutic Findings

Mitochondrial respiration restricts Listeria monocytogenes infection by slowing down host cell receptor recycling

The immune system as a driver of mitochondrial disease pathogenesis: a review of evidence

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