ReviewJournal of inherited metabolic disease2012
Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases.
Review in Journal of inherited metabolic disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 129 citations in OpenAlex.
- KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers.Orphanet journal of rare diseases · 2017Trial
- Mitochondrial complex I deficiency-associated diseases and models.Cellular and molecular life sciences : CMLS · 2026Review
- Clinical Spectrum, Heteroplasmy-Phenotype Correlation, and Prognosis of the MT-ND3 m.10191 T > C Mutation.CNS neuroscience & therapeutics · 2026Article
- Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Bioenergetic Signatures of DLD Deficiency: Dissecting PDHc- and α-KGDHc-Linked Defects.Antioxidants (Basel, Switzerland) · 2025Article
- Acute profound lactic alkalosis associated withMolecular genetics and metabolism reports · 2025Article
- Clinico-Radiological and Genotypic Spectrum of Nuclear Mitochondriopathies.Indian journal of pediatrics · 2025Article
- NADH Reductive Stress and Its Correlation with Disease Severity in Leigh Syndrome: A Pilot Study Using Patient Fibroblasts and a Mouse Model.Biomolecules · 2024Article
- Disease models of Leigh syndrome: From yeast to organoids.Journal of inherited metabolic disease · 2024Review
- Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant.Movement disorders clinical practice · 2024Article
- Alternative splicing expands the clinical spectrum of NDUFS6-related mitochondrial disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Pathways controlling neurotoxicity and proteostasis in mitochondrial complex I deficiency.Human molecular genetics · 2024Article
- Efficacy and Safety of Ketogenic Diet Treatment in Pediatric Patients with Mitochondrial Disease.Nutrients · 2024Article
- A Drosophila model of mitochondrial disease phenotypic heterogeneity.Biology open · 2024Article
- Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4The EMBO journal · 2024Article
- Clinical Reasoning: A 14-Year-Old Girl With Reversible Peripheral Neuropathy and Encephalopathy.Neurology · 2023Article
- Article
- Yeast NDI1 reconfigures neuronal metabolism and prevents the unfolded protein response in mitochondrial complex I deficiency.PLoS genetics · 2023Article
- A Novel Mutation Associated with Neonatal Lethal Cardiomyopathy Leads to an Alternative Transcript Expression in the X-Linked Complex IInternational journal of molecular sciences · 2023Article
- Early-onset leukoencephalomyelopathy due to a biallelic NDUFV1 variant in a mid-forties patient.Annals of clinical and translational neurology · 2022Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 12 institutions in 9 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial complex I is the largest multi-protein enzyme complex of the oxidative phosphorylation system. Seven subunits of this complex are encoded by the mitochondrial and the remainder by the nuclear genome. We review the natural disease course and signs and symptoms of 130 patients (four new cases and 126 from literature) with mutations in nuclear genes encoding structural complex I proteins or those involved in its assembly. Complex I deficiency caused by a nuclear gene defect is usually a non-dysmorphic syndrome, characterized by severe multi-system organ involvement and a poor prognosis. Age at presentation may vary, but is generally within the first year of life. The most prevalent symptoms include hypotonia, nystagmus, respiratory abnormalities, pyramidal signs, dystonia, psychomotor retardation or regression, failure to thrive, and feeding problems. Characteristic symptoms include brainstem involvement, optic atrophy and Leigh syndrome on MRI, either or not in combination with internal organ involvement and lactic acidemia. Virtually all children ultimately develop Leigh syndrome or leukoencephalopathy. Twenty-five percent of the patients died before the age of six months, more than half before the age of two and 75 % before the age of ten years. Some patients showed recovery of certain skills or are still alive in their thirties . No clinical, biochemical, or genetic parameters indicating longer survival were found. No clear genotype-phenotype correlations were observed, however defects in some genes seem to be associated with a better or poorer prognosis, cardiomyopathy, Leigh syndrome or brainstem lesions.
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