What's in a name?
What does LHON stand for?
Leber Hereditary Optic Neuropathy
Is LHON caused by a variant in the mtDNA or nuclear DNA?
Bonus: What is/are the most common gene(s) affected?
mtDNA
Bonus: MT-ND1, MT-ND4, MT-ND6
Part of Complex I of the ETC
What population is most commonly affected by LHON?
Young men
What should people with LHON avoid to reduce the risk of vision loss?
Smoking and alcohol
False
What does MELAS stand for?
Mitochondrial encephalopathy, lactic acidosis, and stoke-like episodes
Are the majority of MELAS cases due to variants in mtDNA or nDNA?
80% due to m.3243A>G (MT-TL1), 10% due to m.3271T>C (MT-ND5)
Small proportion of cases d/t nDNA variants
Which mitochondrial disorder is associated with early childhood onset of neurodevelopmental regression, feeding difficulties/vomiting/FTT, hypotonia/dystonia/ataxia, pathologic lesions in the basal ganglia, cerebellum, and/or brainstem, and early death (often due to respiratory failure)?
Leigh syndrome
What treatment is given to someone with MELAS experiencing stroke-like symptoms?
IV arginine
What is heteroplasmy?
The presence of multiple mitochondrial DNA variants within a cell/organism
What does MERRF stand for?
Myoclonic epilepsy with ragged red fibers
Is MERRF caused by variants in nDNA or mtDNA?
mtDNA
Genes that encode tRNA; MT-TK (>90%)
Leads to impaired ability to make proteins in mitochondria
What are the 4 canonic features of MERRF needed to make a clinical diagnosis?
Myoclonus
Generalized epilepsy
Ataxia
Ragged red fibers on muscle biopsy
What treatment is given to someone with Kearns-Sayre syndrome who has low 5-methyltetrahydrofolate in CSF or white matter abnormalities?
Folinic acid
What is the threshold theory?
When the level of mutant mitochondria exceeds a certain threshold, the cell expresses dysfunction
When a cell divides, mitochondria are not distributed equally, so the new cells may have a higher or lower proportion of mutant mitochondria than the progenitor
What does NARP stand for?
Neuropathy, ataxia, and retinitis pigmentosa
Pathogenic variants in which gene cause NARP?
MT-ATP6
mtDNA that encodes a subunit of ATP synthase
What is the Kearsn-Sayre classic clinical triad?
Pigmentary retinopathy
Chronic progressive external ophthalmoplegia including ptosis
Cardiac conduction abnormality
What mitochondrial supplement therapy may be beneficial in treatment general mitochondrial dysfunction?
Coenzyme Q10
Which complex of the ETC is encoded entirely by nuclear DNA?
Complex II
What does CPEO stand for?
Chronic progressive external ophthalmoplegia
Kearns-Sayre syndrome, Pearson syndrome, and CPEO are all caused by this shared underlying genetic mechanism involving the mitochondrial genome.
large-scale mtDNA deletion
Typically de novo
What feature distinguishes Pearson syndrome from Kearns Sayre syndrome and CPEO?
Bone marrow failure - pancytopenia, severe refractory anemia, exocrine pancreatic insufficiency
What is the gold standard therapy for pyruvate dehydrogenase deficiecy?
Ketogenic diet (low-carb)
What are ragged red fibers?
Accumulation of excess mitochondria seen on muscle biopsy - body is trying to compensate for lack of energy or non-working mitochondria
This is not diagnostic