Term
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Definition
100s to 1000s in all cells except RBCs
Maternally inherited
Have their own genome |
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Term
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Definition
Contains 27 genes
Encode for tRNA, rRNA, and components of the ETC
mtDNA has higher mutation rate because there are less repair mechanisms |
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Term
| Inheritance pattern of mtDNA |
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Definition
Maternally inherited
Mothers give mtDNA to all offspring |
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Term
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Definition
May present at different ages
Extreme clinical heterogeneity
May affect any organ/tissues - most severe in metabolically active tissues such as brain, liver, and muscle
Usually exacerbated by stress such as fasting, infection, etc |
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Term
| Diagnosing mitochondrial diseases |
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Definition
First step: suspicion
Any progressive multisystem disorder with neurologic symptoms could be mito related |
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Term
| Specific testing for mito diseases |
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Definition
Plasma lactate
Plasma AAs
Neuroimaging
Muscle biopsy - most accurate because you can directly measure ox phos activity |
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Term
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Definition
Mitochondrial encephalopathy, lactic acidosis, stroke like symptoms
Develop neuro symptoms first, followed by lactic acidosis and then myopathy
Usually caused by mtDNA mutations
80% of the time mutation in MT-TL1 gene which encodes a tRNA |
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Term
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Definition
"mitochondrial cocktail" - CoQ, creatine, lipoic acid
Arginine can be given during acute stroke like events - acts as NO donor |
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Term
| Pyruvate dehydrogenase deficiency |
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Definition
Psychomotor retardation, hypotonia, progressive encephalopathy, brain malformation
X linked inheritance
Treatment: ketogenic diet to give alternate path for acetylCoA production |
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Term
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Definition
AKA subacute necrotizing encephalomyelopathy
Progressive neurodegenerative disorder that develops around 3-12 months of age with environmental trigger
Clinically: psychomotor regression, hypotonia, chorea, ataxia, peripheral neuropathy, cardiomyopathy
Patients usually die around 2-3 years old |
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Term
| Diagnostic criteria for Leigh syndrome |
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Definition
Progressive neurologic disease with motor and intellectual delay
Brainstem and basal ganglia disease
Elevated lactate in blood or CSF
Imaging: typical LD features on neuroimaging including multiple symmetric focal necrotic lesions |
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Term
| Mutations involved in Leigh syndrome |
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Definition
Many different genes that encode for different complexes of the electron transport chain
Most are mitochondrially inherited |
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Term
| Genotype/Phenotypes of Leigh syndrome |
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Definition
T8993G: Mutant load <60% asymptomatic, 70-90% have NARP (peripheral neuropathy, ataxia, RP), >90% have Leigh
T8993C: Mutant load <90% asymptomatic, >90% affected |
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Term
| Management of Leigh syndrome |
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Definition
No specific treatment
Give sodium bicarb to reverse acidosis (due to elevated lactate)
Give antiepileptics (not valproate or barbituates)
Mitochondrial cocktail can be given but with little effect
Hospice care |
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Term
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Definition
Continuum of overlapping phenotypes - vary in severity, age of onset, organ specificity
POLG1 is a nuclear gene that is responsible for mtDNA repair mechanisms |
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Term
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Definition
Severe and progressive encephalopathy - cortex is affected more than brainstem/basal ganglia
Seizures often first symptom
Age of onset is variable, normally around 2-4 years
Liver dysfunction follows |
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Term
| Childhood myocerebrohepatopathy |
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Definition
POLG1
Seizures, neurologic regression, liver dysfunction, myopathy
Less severe version of Alpers |
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Term
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Definition
POLG1
Myoclonic epilepsy myopathy sensory ataxia |
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Term
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Definition
POLG1
Ataxia neuropathy spectrum |
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Term
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Definition
POLG1
AR and AD progressive external ophthalmoplegia |
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Term
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Definition
Alpers
Childhood myocerebrohepatopathy
MEMSA
ANS
AR and AD PEO |
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Term
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Definition
| Nuclear gene that encodes for Pol gamma 1 which is important for mtDNA replication/repair |
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Term
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Definition
Mitochondrial neurogastrointestinal encephalopathy
Symptoms start in adolescence
GI symptoms, peripheral neuropathy, ophthalmoplegia/ptosis |
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Term
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Definition
Caused by thymidine phosphorylase deficiency
AR inheritance, nuclear encoded, cytoplasmic
Leads to massive elevations of thymidine which disrupts the mtDNA replication system (lots of mutations in mtDNA) |
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