Mito

Question 1

Kearns-Sayre syndrome

Answer 1

heteroplasmic ~5kb del in mtDNA
progressive myopathy, PEO, ptosis, cardiomyopathy (this combo is specific)
usually sporadic, early onset, death in young adulthood

Question 2

Myoclonic epilepsy w/ Ragged Red Fibers (MERRF)

Answer 2

heteroplasmic tRNA (lys) gene
myopathy, dementia, ataxia, myoclonic seizures, deafness
activity of complex I & IV reduced

Question 3

Leber hereditary optic neuropathy (LHON)

Answer 3

homoplasmic SNV in NADH dehydrogenase genes (ND)
sudden central vision loss due to optic nerve atrophy
male bias> modifier loci on X chr

Question 4

Leigh syndrome

Answer 4

mtDNA or nuclear (nuclear more common)
nuclear can be AR (SURF1, complex I,II,III,IV) or XL (PDH)
mtDNA: heteroplasmic ATPase 6 gene
early onset neurodegeneration: hypotonia, DD, optic atriphy, basal ganglia disease; rapidly fatal
elevated Lactate

Question 5

Neurogenic muscle weakness, ataxia, RP (NARP)

Answer 5

attenuated form of Leigh syndrome
caused by lower heteroplasmy of mtDNA variants

Question 6

Mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes (MELAS)

Answer 6

stroke like episodes are buzzword
seizures, neuropathy, SNHL, lactic acidosis
heteroplasmic tRNA (leu) gene
leucine tRNA MT-TL1 m.3243A>G is most common
same variant can cause a more classic mito phenotyep too though