Table 1

Genetic classification of the mitochondrial respiratory chain diseases

Genetic defectPhenotype
Defects in mtDNA
    Mutations in protein-coding genes
        Mitochondrial complex I (ND) genesLHON, MELAS, Leigh syndrome
        Mitochondrial complex V (ATPase) genesNARP, Leigh syndrome
    Mutations in protein synthesis genes
        tRNA genesPEO, myopathy MELAS, MERRF
        rRNA genesDeafness
        RearrangementsMyopathy, PEO, KSS
Defects in nuclear genes
    Defects in mtDNA replication
        PEO1AD PEO
        SLC25A4AD PEO
    Defects in respiratory chain subunit genes
        Complex I, II, III or IVEncephalomyopathies
    Defects in respiratory chain assembly
        Complex I, eg, NDUFAF1Encephalomyopathy and cardiomyopathy
        Complex III BCS1LBjornstad syndrome (SNHL and pili torti)
        Complex IV, eg, SURF1Leigh syndrome
    Defects in mitochondrial dynamics
        OPA1AD optic atrophy, auditory neuropathy, peripheral neuropathy
    Defects in coenzyme Q10 biosynthesis,
        eg, CABC1Cerebellar ataxia, exercise intolerance, seizures
    Defects in mitochondrial translation
        Aminoacyl tRNA synthetases, eg, DARS2LBSL
        tRNA modification, eg, PUS1Myopathy, sideroblastic anaemia, lactic acidosis
    Defects in mitochondrial import
        TIMM8ADeafness dystonia syndrome
        SLC25A3Cardiomyopathy, hypotonia, growth retardation
    Defects in mitochondrial membrane lipids
        Tafazzin proteinBarth syndrome (cardiomyopathy)
  • AD, autosomal dominant; AR, autosomal recessive; KSS, Kearns–Sayre syndrome; LBSL, leucoencephalopathy with bilateral striatal involvement and lactate accumulation; LHON, Leber hereditary optic neuropathy; LS, Leigh syndrome; MELAS, mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes; MERRF, myoclonus epilepsy with ragged red fibres; MNGIE, mitochondrial neurogastrointestinal encephalomyopathy; NARP, neuropathy, ataxia and retinitis pigmentosa; PEO, progressive external ophthalmoplegia; SNHL, sensorineural hearing loss.