Mitochondrial Disorders Flashcards
How many genes make up mitochondrial DNA
37 Genes
How is mitochondrial DNA organized
double stranded ring, no introns, no homologous recombination or meiosis
The majority of genes that contribute to the ETC come from _ DNA
nuclear
Which complex of the ETC is entirely nuclear encoded
Complex II
How many nuclear genes contribute to mitochondrial function
over 1200
Leigh syndrome is also referred to as
Subacute necrotizing encephalomyelopathy
Leigh syndrome is characterized by
the degeneration of the central nervous system (brain, spinal cord, and optic nerve)
Clinical features of Leigh syndrome
Leukodystrophy on MRI
DD/ regression
Ataxia, spasticity, hypotonia
neuropathy
nystagmus
opthalmoparesis
optic atrophy, RP
dysphagia
HCM
Deafness
Onset of Leigh syndrome
3-12 months
Genes associated with Leigh Syndrome
> 75
most common: SURF1
MTATP6, PDHA1, BTD
NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) Clinical features
Salt and pepper retinopathy
DD
Numbness, tingling or pain in the extremities
Balance/coordination problems
Proximal muscle weakness
vision loss/light sensitivity
hearing loss
seizures
cardiac conduction defects
Onset for NARP
Adolescence or young adulthood
High levels of heteroplasmy with NARP may cause
Leigh syndrome
MELAS
Mitochondrial encephalopathy, Lactic Acidosis, and Stroke-Like Episodes
Clinical features of MELAS
“Stroke-like” episodes: seizures, headaches, encephalopathy, dementia
elevated lactic acid in blood and CSF
muscle weakness, exercise intolerance
cortical vision loss
hemiparesis
vomiting
hearing loss
short stature
DM
Peripheral neuropathy
MELAS MRI
do not have the classic vascular findings as in stroke
asymmetric, increased T2 signal
typically, posterior cerebrum
Leigh syndrome MRI
Bilateral, symmetrical hypintensities in the basal ganglia or brainstem
MIDD
Maternally Inherited Diabetes- Deafness (MIDD)
Clinical features of MIDD
rapid and severe bilateral sensory hearing loss typically in the 20s-30s
DM develop later in the third decade
MIDD is more commonly prevalent in what population
Japanese
this mutation makes up 85% of MIDD cases
m.3243A>G
MERRF
Myoclonic Epilepsy with Ragged Red Fibers
Clinical Features of MERRF
myoclonus, CNS deterioration (seizures, ataxia
Short stature
Cardiomyopathy; dysthymias
hearing loss
ophthalmoplegia
exercise intolerance
peripheral neuropathy
biochemical finding of MERRF
Increased lactate and pyruvate in blood and CSF- increases after exercise
Muscle biopsy finding of MERRF
Ragged red fibers
LHON
Leber Hereditary Optic Nueropathy
LHON clinical features
Vision loss (bilateral blurring and clouding of vision)
tremors, neuropathy
arrhythmia
Common variants for LHON
m.11778G>A, m.3460G>A, m.14484T>C
LHON is more common in
Males
Pearson Syndrome
Sideroblastic anemia,
bone marrow failure
exocrine pancreatic failure
renal fanconi syndrome
lactic acidosis
Key findings for Pearson syndrome
weakness, fatigue, frequent infections, easy bruising, failure to thrive, liver and kidney failure
Kearns Sayre
retinopathy, rod-cone dystrophy, ptosis, ophthalmoplegia
adrenal insufficiency
cardiac conduction defects
ataxia
endocrine dysfunction- diabetes
hypothyroidism
adrenal insufficiency
Sensory neural hearing loss
Failure to thrive
CPEO
Chronic Progressive External Opthalmoplegia
CPEO clinical symptoms
Pstosis
ophthalmoplegia
proximal limb weakness
exercise intolerance, myopathy, dysphagia
MNGIE
Mitochondrial Nuerogastrointestinal Encephalopathy Disease
Clinical features of MNGIE
Dysmotility (nausea, dysphagia, reflux, pain, diarrhea, emesis)
Cachexia
Ptosis/ opthalmoplegia
Leukoencephalotpathy
demyelinating peripheral neuropathy
distal weakness
Onset of MNGIE
variable with mean onset of 18
Gene associated with MNGIE
TYMP
Biochemical marker for MNGIE
elevated plasma thymidine and deoxyuridine or enzymatic analysis of thymidine phosphorylase
POL-G related disorders
alpers-huttenlocher syndrome
childhood myocerebrohepatopathy spectrum
myoclonic epilepsy myopathy sensory ataxia
ataxia neuropathy spectrum
autosomal recessive/ dominant progressive external opthalmoplegia
adult onset non syndromic sensorineural hearing loss gene
MT-RNR1
childhood onset non syndromic sensiorneural hearing loss gene
MT-TS1
Complex II deficiencies genes
SDHA, SDHB, SDHC, SDHD
heteroplasmy increases in
rapidly dividing cells
when seeing older patients its is useful to test
fibroblasts
most common tissues to test
fibroblasts, muscle, hear, liver
