Mitochondrial

Question 1

Traits that should trigger screening for mitochondrial disease

Answer 1

Hearing loss in 30s + diabetes, chronic progressive external ophthalmoplegia

Question 2

Stroke-like episodes. Can include deafness, DM, pigmentary retinopathy, cardiomyopathy, ataxia, seizures, lactic acidosis, myopathy.

Answer 2

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

Question 3

Progressive myoclonic epilepsy, ataxia, weakness, lipomas around neck, hyperlipidemia w/o CV risk, WPW syndrome, hearing loss, lactic acidosis, retinopathy.

Answer 3

Myoclonic epilepsy with ragged red fibers (MERRF): m.8344A>G in MT-TK and other mtDNA variants as well.

Question 4

Childhood onset but often quiescent until adulthood: sensorimotor neuropathy, ataxia, retinopathy. + Sz, ID/demential, proximal weakness, hearing loss, conduction defects.

Answer 4

Neurogenic muscle weakness, ataxia, and Retinitis Pigmentosa (NARP): m.8993T>G in MT-ATP6, a few other variants. Continuum with Leigh syndrome.

Question 5

m3243 differential diagnosis

Answer 5

MELAS, MERRF, maternally inherited diabetes and deafness (MIDD), enteropathy, HCM, cluster headaches; highly variable

Question 6

Infant/child with episodes of developmental regression followed by partial recovery, hypotonia/dystonia, dysphagia, epilepsy, FTT.

Answer 6

Leigh syndrome: >75 genes, nDNA and mtDNA

Question 7

Child w/intractable epilepsy, loss of milestones, liver disease.

Answer 7

Alpers-Huttenlocher syndrome; most in POLG. Several other diseases in spectrum a/w neuropathy, movement disorders, epilepsy.

Question 8

Congenital cataracts, HCM, exercise intolerance/myopathy, lactic acidosis.

Answer 8

Sengers syndrome: AGK (nuclear)

Question 9

Hearing loss, encephalopathy, FTT< hypotonia, DD, spasticity, hypoglycemia, hepatopathy, lactic acidosis

Answer 9

MEGDEL syndrome (3-methylglutaconic acuduria w/deafness, encephalopathy, and Leigh-like syndrome): SERAC1 (nuclear)

Question 10

Child w/sideroblastic anemia, pancreatic dysfunction (exocrine and/or endocrine) pancytopenia, renal tubulopathy.

Answer 10

Pearson syndrome: large deletions or rearrangements of mtDNA

Question 11

Child w/progressive neuromuscular weakness & lactic acidosis, often fatal.

Answer 11

Congenital lactic acidosis: nuclear or mitochondrial missense variants

Question 12

Adult w/subacute painless bilateral vision loss.

Answer 12

Leber hereditary optic neuropathy, LHON: several mtDNA variants incl m.11778G>A, m.14484T>C, m.3460G>A

Question 13

Pigmentary retinopathy w/progressive vision loss, ataxia, cardiac conduction abnormalities, DM, deafness, bulbar weakness, dementia.

Answer 13

Kearns-Sayre syndrome (KSS): large mtDNA deletion

Question 14

Chronic progressive external ophthalmoplegia in older adults

Answer 14

C10orf2 (Twinkle) if isolated, MANY other genes associated with a variety of other symptoms

Question 15

Gastrointestinal dysmotility, muscle weakness/atrophy, ophthalmoplegia, neuropathy, retinopathy, hearing loss

Answer 15

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) syndrome: TYMP, RRM2B, and POLG variants

Question 16

Drugs to avoid w/mitochondrial disease

Answer 16

Valproic acid, ahminoglycosides

Question 17

Use of ketogenic diet in mitochondrial diseases w/epilepsy

Answer 17

Only for pyruvate dehydrogenase deficiency, otherwise worsens neuropathy