scholarly journals Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation

2017 ◽  
pp. 37-43 ◽  
Author(s):  
Francesca Minoia ◽  
Marta Bertamino ◽  
Paolo Picco ◽  
Mariasavina Severino ◽  
Andrea Rossi ◽  
...  
Keyword(s):  
Leigh Syndrome

Leigh Syndrome: typical phenotype but atypical mitochondrial mutation – a case report

2010 ◽  
Vol 41 (02) ◽  
Author(s):  
K Lengnick ◽  
O Hasselmann ◽  
R Horváth ◽  
B Schoser ◽  
J Mayr ◽  
...  
Keyword(s):  
Case Report ◽  
Leigh Syndrome ◽  
Mitochondrial Mutation

Biotin-responsive basal ganglia disease: a treatable differential diagnosis of Leigh syndrome

2013 ◽  
Vol 44 (02) ◽  
Author(s):  
F Distelmaier ◽  
P Huppke ◽  
J Schaper ◽  
E Morava ◽  
E Mayatepek ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Basal Ganglia ◽  
Leigh Syndrome ◽  
Basal Ganglia Disease

scholarly journals Hypoxia ameliorates brain hyperoxia and NAD+ deficiency in a murine model of Leigh syndrome

2021 ◽  
Vol 133 (1) ◽  
pp. 83-93
Author(s):  
Robert M.H. Grange ◽  
Rohit Sharma ◽  
Hardik Shah ◽  
Bryn Reinstadler ◽  
Olga Goldberger ◽  
...  
Keyword(s):  
Murine Model ◽  
Leigh Syndrome

scholarly journals Ndufs4 ablation decreases synaptophysin expression in hippocampus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Subrata Kumar Shil ◽  
Yoshiteru Kagawa ◽  
Banlanjo Abdulaziz Umaru ◽  
Fumika Nanto-Hara ◽  
Hirofumi Miyazaki ◽  
...  
Keyword(s):  
Nadh Dehydrogenase ◽  
Leigh Syndrome ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Activity ◽  
Mitochondrial Complex ◽  
Neuronal Function ◽  
Mouse Hippocampus ◽  
Extracellular Regulated Kinase ◽  
Presynaptic Protein

AbstractAltered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.

SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Francesco Porta ◽  
Barbara Siri ◽  
Nicoletta Chiesa ◽  
Federica Ricci ◽  
Lulash Nika ◽  
...  
Keyword(s):  
Axonal Neuropathy ◽  
Clinical Signs ◽  
Leigh Syndrome ◽  
High Dose ◽  
New Variant ◽  
Long Term Follow Up ◽  
Basal Ganglia Involvement ◽  
Biallelic Mutations ◽  
Thiamine Treatment ◽  
Striatal Necrosis

AbstractObjectivesBiallelic mutations in the SLC25A19 gene impair the function of the thiamine mitochondrial carrier, leading to two distinct clinical phenotypes. Homozygosity for the c.530G > C mutation is invariably associated to Amish lethal microcephaly. The second phenotype, reported only in 8 patients homozygous for different non-Amish mutations (c.373G > A, c.580T > C, c.910G > A, c.869T > A, c.576G > C), is characterized by bilateral striatal necrosis and peripheral polyneuropathy. We report a new patient with the non-Amish SLC25A19 phenotype showing compound heterozygosity for the new variant c.673G > A and the known mutation c.373G > A.Case presentationThe natural history of non-Amish SLC25A19 deficiency is characterized by acute episodes of fever-induced encephalopathy accompanied by isolated lactic acidosis and Leigh-like features at magnetic resonance imaging (MRI). Acute episodes are prevented by high-dose thiamine treatment (600 mg/day). As shown in the new case, both mild clinical signs and basal ganglia involvement can precede the acute encephalopathic onset of the disease, potentially allowing treatment anticipation and prevention of acute brain damage. Peripheral axonal neuropathy, observed in 7 out of 9 patients, is not improved by thiamine therapy. In two early treated patients, however, peripheral neuropathy did not occur even on long-term follow-up, suggesting a potential preventive role of treatment anticipation also at the peripheral level.ConclusionsNon-Amish SLC25A19 deficiency is an extra-rare cause of Leigh syndrome responsive to thiamine treatment. Ex adiuvantibus thiamine treatment is mandatory in any patient with Leigh-like features.

scholarly journals TAT-Conjugated NDUFS8 Can Be Transduced into Mitochondria in a Membrane-Potential-Independent Manner and Rescue Complex I Deficiency

2021 ◽  
Vol 22 (12) ◽  
pp. 6524
Author(s):  
Bo-Yu Lin ◽  
Gui-Teng Zheng ◽  
Kai-Wen Teng ◽  
Juan-Yu Chang ◽  
Chao-Chang Lee ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Fusion Proteins ◽  
Complex I ◽  
Nadh Dehydrogenase ◽  
Leigh Syndrome ◽  
Protein Transduction ◽  
Independent Manner ◽  
Complex I Deficiency ◽  
Transactivator Of Transcription ◽  
Hiv 1

NADH dehydrogenase (ubiquinone) Fe-S protein 8 (NDUFS8) is a nuclear-encoded core subunit of human mitochondrial complex I. Defects in NDUFS8 are associated with Leigh syndrome and encephalomyopathy. Cell-penetrating peptide derived from the HIV-1 transactivator of transcription protein (TAT) has been successfully applied as a carrier to bring fusion proteins into cells without compromising the biological function of the cargoes. In this study, we developed a TAT-mediated protein transduction system to rescue complex I deficiency caused by NDUFS8 defects. Two fusion proteins (TAT-NDUFS8 and NDUFS8-TAT) were exogenously expressed and purified from Escherichia coli for transduction of human cells. In addition, similar constructs were generated and used in transfection studies for comparison. The results showed that both exogenous TAT-NDUFS8 and NDUFS8-TAT were delivered into mitochondria and correctly processed. Interestingly, the mitochondrial import of TAT-containing NDUFS8 was independent of mitochondrial membrane potential. Treatment with TAT-NDUFS8 not only significantly improved the assembly of complex I in an NDUFS8-deficient cell line, but also partially rescued complex I functions both in the in-gel activity assay and the oxygen consumption assay. Our current findings suggest the considerable potential of applying the TAT-mediated protein transduction system for treatment of complex I deficiency.

Orbital rhabdomyosarcoma in a child with Leigh syndrome

2018 ◽  
Vol 22 (2) ◽  
pp. 150-152.e1 ◽  
Author(s):  
Ang Li ◽  
Alexander Blandford ◽  
Rao V. Chundury ◽  
Elias I. Traboulsi ◽  
Peter Anderson ◽  
...  
Keyword(s):  
Leigh Syndrome

Leigh syndrome and partial deficit of cytochrome c oxidase associated with epilepsia partialis continua

1996 ◽  
Vol 18 (3) ◽  
pp. 207-211 ◽  
Author(s):  
Maurizio Elia ◽  
Sebastiano Antonino Musumeci ◽  
Raffaele Ferri ◽  
Vito Colamaria ◽  
Gaetano Azan ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Leigh Syndrome ◽  
Epilepsia Partialis Continua
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