Mitochondrial Flashcards
Traits that should trigger screening for mitochondrial disease
Hearing loss in 30s + diabetes, chronic progressive external ophthalmoplegia
Stroke-like episodes. Can include deafness, DM, pigmentary retinopathy, cardiomyopathy, ataxia, seizures, lactic acidosis, myopathy.
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): 24 variants in MT-TL1 (e.g. m.3243A>G), other mtDNA variants as well
Progressive myoclonic epilepsy, ataxia, weakness, lipomas around neck, hyperlipidemia w/o CV risk, WPW syndrome, hearing loss, lactic acidosis, retinopathy.
Myoclonic epilepsy with ragged red fibers (MERRF): m.8344A>G in MT-TK and other mtDNA variants as well.
Childhood onset but often quiescent until adulthood: sensorimotor neuropathy, ataxia, retinopathy. + Sz, ID/demential, proximal weakness, hearing loss, conduction defects.
Neurogenic muscle weakness, ataxia, and Retinitis Pigmentosa (NARP): m.8993T>G in MT-ATP6, a few other variants. Continuum with Leigh syndrome.
m3243 differential diagnosis
MELAS, MERRF, maternally inherited diabetes and deafness (MIDD), enteropathy, HCM, cluster headaches; highly variable
Infant/child with episodes of developmental regression followed by partial recovery, hypotonia/dystonia, dysphagia, epilepsy, FTT.
Leigh syndrome: >75 genes, nDNA and mtDNA
Child w/intractable epilepsy, loss of milestones, liver disease.
Alpers-Huttenlocher syndrome; most in POLG. Several other diseases in spectrum a/w neuropathy, movement disorders, epilepsy.
Congenital cataracts, HCM, exercise intolerance/myopathy, lactic acidosis.
Sengers syndrome: AGK (nuclear)
Hearing loss, encephalopathy, FTT< hypotonia, DD, spasticity, hypoglycemia, hepatopathy, lactic acidosis
MEGDEL syndrome (3-methylglutaconic acuduria w/deafness, encephalopathy, and Leigh-like syndrome): SERAC1 (nuclear)
Child w/sideroblastic anemia, pancreatic dysfunction (exocrine and/or endocrine) pancytopenia, renal tubulopathy.
Pearson syndrome: large deletions or rearrangements of mtDNA
Child w/progressive neuromuscular weakness & lactic acidosis, often fatal.
Congenital lactic acidosis: nuclear or mitochondrial missense variants
Adult w/subacute painless bilateral vision loss.
Leber hereditary optic neuropathy, LHON: several mtDNA variants incl m.11778G>A, m.14484T>C, m.3460G>A
Pigmentary retinopathy w/progressive vision loss, ataxia, cardiac conduction abnormalities, DM, deafness, bulbar weakness, dementia.
Kearns-Sayre syndrome (KSS): large mtDNA deletion
Chronic progressive external ophthalmoplegia in older adults
C10orf2 (Twinkle) if isolated, MANY other genes associated with a variety of other symptoms
Gastrointestinal dysmotility, muscle weakness/atrophy, ophthalmoplegia, neuropathy, retinopathy, hearing loss
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) syndrome: TYMP, RRM2B, and POLG variants