Mitochondrial complex I deficiency, nuclear type 1

Preferred Label : Mitochondrial complex I deficiency, nuclear type 1;

Symbol : MC1DN1;

CISMeF acronym : MC1DN1;

Type : Phenotype, molecular basis known;

Alternative titles and symbols : Nadh:q(1) oxidoreductase deficiency; Mitochondrial nadh dehydrogenase component of complex I, deficiency of; Nadh-coenzyme q reductase deficiency; Mitochondrial complex I deficiency;

Description : Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (256000), Leber hereditary optic neuropathy (535000), and some forms of Parkinson disease (see 556500) (Loeffen et al., 2000; Pitkanen et al., 1996; Robinson, 1998). - Genetic Heterogeneity of Complex I Deficiency Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible (summary by Haack et al., 2012). However, the majority of cases are caused by mutations in nuclear-encoded genes (Loeffen et al., 2000; Triepels et al., 2001). Complex I deficiency with autosomal recessive inheritance results from mutation in nuclear-encoded subunit genes, including NDUFV1 (161015),;

Inheritance : Autosomal recessive;

Molecular basis : Caused by mutation in the NADH-ubiquinone oxidoreductase subunit S4 gene (NDUFS4, 602694.0001);

Laboratory abnormalities : Lactic acidemia; Increased CSF lactate; Decreased activity of mitochondrial respiratory chain complex I in various tissues;

Prefixed ID : #252010;

Details

Origin ID

252010;

UMLS CUI

C1838979;

CISMeF manual mappings
- complex I deficiency [Disease (Nov.)]
Currated CISMeF NLP mapping
- Isolated complex I deficiency [ORDO Disease]
- Mitochondrial complex I deficiency [MeSH concept]
- Nicotinamide adenine dinucleotide coenzyme Q reductase deficiency (disorder) [SNOMED CT concept]
- mitochondrial complex I deficiency [DO Concept]
- mitochondrial complex I deficiency [MeSH Supplementary Concept]
DO Cross reference
- mitochondrial complex I deficiency [DO Concept]
Genes related to phenotype
- Nadh-ubiquinone oxidoreductase fe-s protein 4 [OMIM gene]
HPO term(s)
- 3-hydroxydicarboxylic aciduria [HPO term]
- Acute necrotizing encephalopathy [HPO term]
- Apnea [HPO term]
- Ataxia [HPO term]
- Autosomal recessive inheritance [HPO term]
- Babinski sign [HPO term]
- Bilateral tonic-clonic seizure [HPO term]
- Blindness [HPO term]
- Cerebellar atrophy [HPO term]
- Cerebral edema [HPO term]
- Coma [HPO term]
- Concentric hypertrophic cardiomyopathy [HPO term]
- Cyanosis [HPO term]
- Death in infancy [HPO term]
- Decreased activity of mitochondrial complex I [HPO term]
- Decreased activity of mitochondrial complex III [HPO term]
- Developmental regression [HPO term]
- Dyskinesia [HPO term]
- Elevated lactate:pyruvate ratio [HPO term]
- Epilepsy [HPO term]
- Exercise intolerance [HPO term]
- Failure to thrive [HPO term]
- Feeding difficulties [HPO term]
- Feeding difficulties in infancy [HPO term]
- Focal T2 hyperintense basal ganglia lesion [HPO term]
- Focal T2 hypointense basal ganglia lesion [HPO term]
- Global developmental delay [HPO term]
- Growth delay [HPO term]
- Hepatic failure [HPO term]
- Hepatomegaly [HPO term]
- Hyperalaninemia [HPO term]
- Hyperreflexia [HPO term]
- Hypertrophic cardiomyopathy [HPO term]
- Hypoglycemia [HPO term]
- Hyporeflexia [HPO term]
- Hypospadias [HPO term]
- Hypotonia [HPO term]
- Increased CSF lactate [HPO term]
- Increased CSF protein [HPO term]
- Increased intramyocellular lipid droplets [HPO term]
- Infantile onset [HPO term]
- Lactic acidosis [HPO term]
- Lacticaciduria [HPO term]
- Lethargy [HPO term]
- Leukodystrophy [HPO term]
- Leukoencephalopathy [HPO term]
- Microcephaly [HPO term]
- Mitochondrial inheritance [HPO term]
- Muscle weakness [HPO term]
- Nystagmus [HPO term]
- Optic disc pallor [HPO term]
- Optic neuropathy [HPO term]
- Poor eye contact [HPO term]
- Poor head control [HPO term]
- Progressive macrocephaly [HPO term]
- Psychomotor regression [HPO term]
- Ptosis [HPO term]
- Ragged-red muscle fibers [HPO term]
- Respiratory failure [HPO term]
- Respiratory insufficiency [HPO term]
- Sensorineural hearing impairment [HPO term]
- Severe lactic acidosis [HPO term]
- Short chin [HPO term]
- Skeletal muscle atrophy [HPO term]
- Spasticity [HPO term]
- Splenomegaly [HPO term]
- Strabismus [HPO term]
- Tongue fasciculations [HPO term]
- Undetectable visual evoked potentials [HPO term]
- Upslanted palpebral fissure [HPO term]
- Vomiting [HPO term]
ORDO concept(s)
- Fatal infantile hypertrophic cardiomyopathy due to mitochondrial complex I deficiency [ORDO Disease]
- Isolated complex I deficiency [ORDO Disease]
- Leigh syndrome with leukodystrophy [ORDO Disease]
See also inter- (CISMeF)
- Fatal infantile hypertrophic cardiomyopathy due to mitochondrial complex I deficiency [ORDO Disease]
Semantic type(s)
- Disease or Syndrome [UMLS semantic type]
UMLS correspondences (same concept)
- Mitochondrial complex I deficiency [MeSH concept]
- Nicotinamide adenine dinucleotide coenzyme Q reductase deficiency (disorder) [SNOMED CT concept]
- mitochondrial complex I deficiency [MeSH Supplementary Concept]
- mitochondrial complex I deficiency [DO Concept]

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