Mitochondrial Disorders

Question 1

How many genes make up mitochondrial DNA

Answer 1

37 Genes

Question 2

How is mitochondrial DNA organized

Answer 2

double stranded ring, no introns, no homologous recombination or meiosis

Question 3

The majority of genes that contribute to the ETC come from _ DNA

Answer 3

nuclear

Question 4

Which complex of the ETC is entirely nuclear encoded

Answer 4

Complex II

Question 5

How many nuclear genes contribute to mitochondrial function

Answer 5

over 1200

Question 6

Leigh syndrome is also referred to as

Answer 6

Subacute necrotizing encephalomyelopathy

Question 7

Leigh syndrome is characterized by

Answer 7

the degeneration of the central nervous system (brain, spinal cord, and optic nerve)

Question 8

Clinical features of Leigh syndrome

Answer 8

Leukodystrophy on MRI
DD/ regression
Ataxia, spasticity, hypotonia
neuropathy
nystagmus
opthalmoparesis
optic atrophy, RP
dysphagia
HCM
Deafness

Question 9

Onset of Leigh syndrome

Answer 9

3-12 months

Question 10

Genes associated with Leigh Syndrome

Answer 10

> 75
most common: SURF1
MTATP6, PDHA1, BTD

Question 11

NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) Clinical features

Answer 11

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

Question 12

Onset for NARP

Answer 12

Adolescence or young adulthood

Question 13

High levels of heteroplasmy with NARP may cause

Answer 13

Leigh syndrome

Question 14

MELAS

Answer 14

Mitochondrial encephalopathy, Lactic Acidosis, and Stroke-Like Episodes

Question 15

Clinical features of MELAS

Answer 15

“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

Question 16

MELAS MRI

Answer 16

do not have the classic vascular findings as in stroke
asymmetric, increased T2 signal
typically, posterior cerebrum

Question 17

Leigh syndrome MRI

Answer 17

Bilateral, symmetrical hypintensities in the basal ganglia or brainstem

Question 18

MIDD

Answer 18

Maternally Inherited Diabetes- Deafness (MIDD)

Question 19

Clinical features of MIDD

Answer 19

rapid and severe bilateral sensory hearing loss typically in the 20s-30s
DM develop later in the third decade

Question 20

MIDD is more commonly prevalent in what population

Answer 20

Japanese

Question 21

this mutation makes up 85% of MIDD cases

Answer 21

m.3243A>G

Question 22

MERRF

Answer 22

Myoclonic Epilepsy with Ragged Red Fibers

Question 23

Clinical Features of MERRF

Answer 23

myoclonus, CNS deterioration (seizures, ataxia
Short stature
Cardiomyopathy; dysthymias
hearing loss
ophthalmoplegia
exercise intolerance
peripheral neuropathy

Question 24

biochemical finding of MERRF

Answer 24

Increased lactate and pyruvate in blood and CSF- increases after exercise

Question 25

Muscle biopsy finding of MERRF

Answer 25

Ragged red fibers

Question 26

LHON

Answer 26

Leber Hereditary Optic Nueropathy

Question 27

LHON clinical features

Answer 27

Vision loss (bilateral blurring and clouding of vision) tremors, neuropathy arrhythmia

Question 28

Common variants for LHON

Answer 28

m.11778G>A, m.3460G>A, m.14484T>C

Question 29

LHON is more common in

Answer 29

Males

Question 30

Pearson Syndrome

Answer 30

Sideroblastic anemia, bone marrow failure exocrine pancreatic failure renal fanconi syndrome lactic acidosis

Question 31

Key findings for Pearson syndrome

Answer 31

weakness, fatigue, frequent infections, easy bruising, failure to thrive, liver and kidney failure

Question 32

Kearns Sayre

Answer 32

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

Question 33

CPEO

Answer 33

Chronic Progressive External Opthalmoplegia

Question 34

CPEO clinical symptoms

Answer 34

Pstosis ophthalmoplegia proximal limb weakness exercise intolerance, myopathy, dysphagia

Question 35

MNGIE

Answer 35

Mitochondrial Nuerogastrointestinal Encephalopathy Disease

Question 36

Clinical features of MNGIE

Answer 36

Dysmotility (nausea, dysphagia, reflux, pain, diarrhea, emesis) Cachexia Ptosis/ opthalmoplegia Leukoencephalotpathy demyelinating peripheral neuropathy distal weakness

Question 37

Onset of MNGIE

Answer 37

variable with mean onset of 18

Question 38

Gene associated with MNGIE

Answer 38

TYMP

Question 39

Biochemical marker for MNGIE

Answer 39

elevated plasma thymidine and deoxyuridine or enzymatic analysis of thymidine phosphorylase

Question 40

POL-G related disorders

Answer 40

alpers-huttenlocher syndrome childhood myocerebrohepatopathy spectrum myoclonic epilepsy myopathy sensory ataxia ataxia neuropathy spectrum autosomal recessive/ dominant progressive external opthalmoplegia

Question 41

adult onset non syndromic sensorineural hearing loss gene

Answer 41

MT-RNR1

Question 42

childhood onset non syndromic sensiorneural hearing loss gene

Answer 42

MT-TS1

Question 43

Complex II deficiencies genes

Answer 43

SDHA, SDHB, SDHC, SDHD

Question 44

heteroplasmy increases in

Answer 44

rapidly dividing cells

Question 45

when seeing older patients its is useful to test

Answer 45

fibroblasts

Question 46

most common tissues to test

Answer 46

fibroblasts, muscle, hear, liver