Late-onset Leigh syndrome due to NDUFV1 mutation in a 10-year-old boy initially presenting with ataxia

İncecik, Faruk; Hergüner, Özlem; Beşen, Şeyda; Bozdoğan, Sevcan Tuğ; Mungan, Neslihan Önenli

doi:10.4103/jpn.jpn_138_17

Cited by 14 publications

(18 citation statements)

References 10 publications

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“…Brain imaging suggested LS, respiratory chain complexes analysis in fibroblasts demonstrated reduced complex I activity confirming WES results. Incecik F. et al confirmed a consanguineous late-onset LS presented with progressive ataxia and dysarthria with normal serum biochemical analysis but abnormal spectroscopy, in which a lactate peak was apparent in both putamen and right caudate topography [24]. NDUFV1 homozygous variants c.1268C > T (p.Thr423Met) were identified pointing to a complex I deficiency.…”

Section: Oxphos Defectsmentioning

confidence: 96%

“…Complex I (ubiquinone oxireductase -NADH): the first mitochondrial complex is known to be the most associated to mutations in mitochondrial diseases, with several LS related genes described so far, being the largest mitochondrial complex involved in ETC [24]. The LS spectrum of presentation is wide regarding the underlying variant, presenting with ataxia, oculomotor apraxia, seizures, neurodevelopmental delay, dystonia, failure to thrive, cardiomyopathy and apnea.…”

Section: Oxphos Defectsmentioning

confidence: 99%

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Molecular basis of Leigh syndrome: a current look

Baldo

Vilarinho

2020

Orphanet J Rare Dis

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Leigh Syndrome (OMIM 256000) is a heterogeneous neurologic disorder due to damage in mitochondrial energy production that usually starts in early childhood. The first description given by Leigh pointed out neurological symptoms in children under 2 years and premature death. Following cases brought some hypothesis to explain the cause due to similarity to other neurological diseases and led to further investigation for metabolic diseases. Biochemical evaluation and specific metabolic profile suggested impairment in energy production (OXPHOS) in mitochondria. As direct approach to involved tissues is not always possible or safe, molecular analysis is a great cost-effective option and, besides biochemical results, is required to confirm the underlying cause of this syndrome face to clinical suspicion. The Next Generation Sequencing (NGS) advance represented a breakthrough in molecular biology allowing simultaneous gene analysis giving short-time results and increasing the variants underlying this syndrome, counting over 75 monogenic causes related so far. NGS provided confirmation of emerging cases and brought up diagnosis in atypical presentations as late-onset cases, which turned Leigh into a heterogeneous syndrome with variable outcomes. This review highlights clinical presentation in both classic and atypical phenotypes, the investigation pathway throughout confirmation emphasizing the underlying genetic heterogeneity and increasing number of genes assigned to this syndrome as well as available treatment.

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Section: Oxphos Defectsmentioning

confidence: 96%

Section: Oxphos Defectsmentioning

confidence: 99%

Molecular basis of Leigh syndrome: a current look

Baldo

Vilarinho

2020

Orphanet J Rare Dis

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“…Oculomotor impairment including ptosis, strabismus, and ophthalmoplegia was also frequently observed. Typical Leigh syndrome [88,107] and late-onset Leigh syndrome have been reported [95,103] . The clinical course was variable with some patients having slower progression of neurological manifestations [90,91,103] .…”

Section: Fdxr Deficiency (Omim #617717)mentioning

confidence: 99%

Riboflavin metabolism: role in mitochondrial function

Balasubramaniam¹,

Yaplito‐Lee²

2020

jtgg

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Riboflavin, known as vitamin B2, a water-soluble vitamin, is an essential nutrient in vertebrates, hence adequate dietary intake is imperative. Riboflavin plays a role in a variety of metabolic pathways, serving primarily as an integral component of its crucial biologically active forms, the flavocoenzymes flavin adenine dinucleotide and flavin mononucleotide. These flavocoenzymes ensure the functionality of numerous flavoproteins including dehydrogenases, oxidases, monooxygenases, and reductases, which play pivotal roles in mitochondrial electron transport chain, β-oxidation of fatty acids, redox homeostasis, citric acid cycle, branched-chain amino acid catabolism, chromatin remodeling, DNA repair, protein folding, and apoptosis. Unsurprisingly, impairment of flavin homeostasis in humans has been linked to various diseases including neuromuscular and neurological disorders, abnormal fetal development, and cardiovascular diseases. This review presents an overview of riboflavin metabolism, its role in mitochondrial function, primary and secondary flavocoenzyme defects associated with mitochondrial dysfunction, and the role of riboflavin supplementation in these conditions.

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“…With interest we read the article by Incecik et al [1] about a 10-year-old boy, born to consanguineous parents, with late-onset Leigh syndrome due to the variant c.1268C>T in the NDUFV1 gene who initially presented with gait ataxia. We have the following comments and concerns.…”

mentioning

confidence: 99%

“…[2] However, Figure 1 of the case report shows asymmetric hyperintensity of the caput of the caudate nucleus. [1] Did hyperintensities of the caudate nucleus become bilaterally symmetric during follow-up?…”

mentioning

confidence: 99%