Isolated complex I deficiency in children: Clinical, biochemical and genetic aspects

Loeffen, Jan; Smeitink, Jan A.M.; Trijbels, J. M. F.; Janssen, A.J.M.; Triepels, R.H.; Sengers, R. C. A.; Heuvel, L.P.W.J. van den

doi:10.1002/(sici)1098-1004(200002)15:2<123::aid-humu1>3.0.co;2-p

Cited by 264 publications

(103 citation statements)

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“…Thirty-nine of these are nuclear-encoded, and at least 13 mutations in these genes have been reported to cause complex I deficiency [25]. The most common neurologic manifestation is Leigh syndrome [26]; other manifestations include cardiomyopathy, hepatopathy, myopathy, encephalomyopathy, tubulopathy, hypotonia, and some forms of Parkinson disease [27,28]. Neuroimaging findings in complex I deficiency includes brainstem lesions with associated basal ganglia lesions, which are hyperintense on T2-weighted images and hypointense on T1-weighted images; leukoencephalopathy; stroke-like lesions; cerebellar hyperintensities [29]; and increased lactate on magnetic resonance spectroscopy.…”

Section: Complex Imentioning

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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Section: Complex Imentioning

confidence: 99%

Mitochondrial Disease in Childhood: Nuclear Encoded

2013

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“…3 It has a wide clinical variety, affecting one or more tissues or organs. 4 The organs with the highest energy demand such as heart, brain, skeletal muscle tissue, and liver are the most affected organs. Owing to the bi-genomic control of the OXPHOS system, mutations causing complex I deficiency can be found in either the mtDNA or in genes encoded by the nuclear DNA.…”

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confidence: 99%

NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease

et al. 2010

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Mitochondrial complex I deficiency is the most common defect of the oxidative phosphorylation system. We report a patient with Leigh syndrome who showed a complex I deficiency expressed in cultured fibroblasts and muscle tissue. To find the genetic cause of the complex I deficiency, we screened the mitochondrial DNA and the nuclear-encoded subunits of complex I. We identified compound-heterozygous mutations in the NDUFA10 gene, encoding an accessory subunit of complex I. The first mutation disrupted the start codon and the second mutation resulted in an amino acid substitution. The fibroblasts of the patient displayed decreased amount and activity, and a disturbed assembly of complex I. These results indicate that NDUFA10 is a novel candidate gene to screen for disease-causing mutations in patients with complex I deficiency.

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“…95 Complex I deficiency is associated with a broad range of clinical phenotypes ranging from lethal neonatal disease to adult onset neurodegenerative disorders. 96,97 A high level of genetic heterogeneity, coupled with weak genotype-phenotype correlations, makes it difficult to predict the genetic basis on pure clinical grounds. 95 This is important because of the different inheritance patterns and different natural histories of the different genetic causes.…”

Section: Disorders Resulting From a Reduction In Mtdna Stabilitymentioning

confidence: 99%

Mitochondrial Genetics

2004

Encyclopedic Dictionary of Genetics, Genomics and Proteomics

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Isolated complex I deficiency in children: Clinical, biochemical and genetic aspects

Cited by 264 publications

References 60 publications

Mitochondrial Disease in Childhood: Nuclear Encoded

Mitochondrial Disease in Childhood: Nuclear Encoded

NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease

Mitochondrial Genetics

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