Mitochondrial disorders

Question 1

Which complex in the respiratory chain complex has no genes encoded by mtDNA?

Answer 1

Complex II

Question 2

What are the general systems impacted in mitochondrial disease?

Answer 2

cardiac
visual impairment
hearing loss
hematologic manifestations
liver dysfunction
renal disease
gastrointestinal problems

Question 3

What does MELAS stand for?

Answer 3

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes

Question 4

Pathology of MELAS

Answer 4

Ragged Red Fibers

Cox-positive

Question 5

Major features of MELAS

Answer 5

stroke-like episodes (migraine-like headaches, cortical blindness, transient hemiplegia, hemaniopia)
lactic acidosis

Question 6

Most common cause of MELAS

Answer 6

80%

A3243G tRNA leu (mtDNA)

Question 7

What does MERFF stand for?

Answer 7

Myoclonic epilepsy with ragged-red fibers

Question 8

Major features of MERRF

Answer 8

myoclonus (sustained muscle contraction)
seixures
ataxia
mild myopathy

Question 9

Pathology of MERFF

Answer 9

Ragged red fibers

cox negative

Question 10

Most common cause of MERFF

Answer 10

80%

A8344G tRNA lys (mtDNA)

Question 11

What does LHON stand for?

Answer 11

Leber hereditary optic neuropathy

Question 12

Major features of LHON

Answer 12

bilateral loss of central vision due to optic atrophy

Question 13

Most common causes of LHON

Answer 13

G11778A in ND4

G3460A in ND1

Question 14

What would I expect a pedigree to look like for a family with LHON?

Answer 14

Maternal inheritance with more affected males

Question 15

Clinical triad of Kearns-Sayre Syndrome

Answer 15

Onset before age 20
CPEO (chronic progressive external ophthalmoplegia)
Retinal degeneration

Question 16

Most common cause of Kearns Sayre syndrome

Answer 16

deletion of mtDNA (5000 bp)

Question 17

Pathology of Kearns Sayre syndrome

Answer 17

RRF

Cox negative

Question 18

Progressive external opthalmoplegia clinical features

Answer 18

isolated ocular myopathy including bilateral ptosis and weakness of the extraocular muscles

Question 19

pathology of progressive external opthalmoplegia

Answer 19

RRF

cox negative

Question 20

Most common cause of chronic external opthalmoplgia

Answer 20

single deletion or duplication of mtDNA

Question 21

What are the general features of mitochondrial depletion syndromes

Answer 21

severe hypotonia, myopathy, liver failure
seizures, opthalmoplegia
very high CPK

all AR, sporadic - no maternal inheritance

Question 22

What are 4 examples of mitochondrial depletion syndromes

Answer 22

MNGIE
Leigh Syndrome
Isolated myopathy
Barth Syndrome

Question 23

What are three examples of disorders of mitochondrial function?

Answer 23

MERFF
MELAS
LHON

Question 24

What are two examples of mitochondrial deletion syndromes?

Answer 24

Kearns Sayre

PEO

Question 25

What does MNGIE stand for?

Answer 25

Mitochondrial neurogastrointestinal encephalopathy

Question 26

Major features of MNGIE

Answer 26

sensorimotor neuropathy
PEO
gastrointestinal dysmotility, nausea, vomiting, diarrhea
see increased thymine levels in the blood
leukodystrophy

AR

Question 27

Leigh syndrome is also called:

Answer 27

subacute necrotizing encephalomopathy

Question 28

Features of Leigh Syndrome

Answer 28

psychomotor retardation
hypotonia, FTT
respiratory abnormalities
oculomotor disturbances
optic atrophy
seizures

often die in childhood

mutations in nDNA or mtDNA

Question 29

Clinical features of Barth Syndrome

Answer 29

dilated cardiomyopathy
neutropenia (low neutrophil count)
growth retardation
muscle weakness

Question 30

What is the inheritance pattern of Barth Syndrome

Answer 30

X-Linked Recessive

Question 31

Important considerations for managing mitochondrial disease

Answer 31

encourage exercise
avoid illness (often get sick more frequently and take longer to recover)
limit general anesthesia

Question 32

What is the RR for mtDNA deletion disorders?

Answer 32

<10% in clinically affected women
prenatal testing is informative
usually de novo