Mitochondrial Disorders

Question 1

LHON

Answer 1

• leber hereditary optic neuropathy
• mtDNA mutation
• low penetrance (M»>F)
• bilateral acute vision loss
• adult onset (avg. age 23y)
• ***majority are homoplasmic
• complex I genes
• can have myopathy/ increased CK
• Ketogenic diet

Question 2

MELAS

Answer 2

• Mitochondiral encephalopathy, lactic acidosis, stroke-like
• mtDNA point mutations
• myopathy w/ RRF
• migraines, psych disorders, dementia, seizures
• endocrine dysfunction
• cardiac involvement

Question 3

Leigh Disease

Answer 3

• mtDNA or nuclear dna mutations
• severe GDD following 3-12mos normal dev.
• lactic acidosis
• seizures
• optic atrophy, oculomotor disturbances
• may have periods of clinical improvement or stability
• death by 2-3 years

Question 4

Kearns-Sayre syndrome

Answer 4

• deletions in mtDNA (usually sporadic)
• clinical triad: onset <20, PEO, retinal degeneration
• must have >1: cardiac conduction defect, elevated CSF protein, ataxia
• other features: SNHL, lactic acidosis, RRF

Question 5

Chronic Progressive External Ophthalmoplegia

Answer 5

• ptosis and progressive opthalmoplegia
• relatively benign
• proximal muscle weakness
• 30% of cases are inherited

Question 6

MERRF

Answer 6

• Myoclonic epilepsy with RRF
• 80% mtDNA point mutations
• 80% inherited
• myoclonus (involuntary twitching)
• seizures
• ataxia
• hearing loss
• optic atrophy

Question 7

Mito disease features

Answer 7

• lactic acidosis
• multi-system involvement: cardiac, GI, vision, hearing, neuro
• regression
• fatigue/exercise intolerance
• temp. instability
• endocrinopathies (diabetes)

Question 8

Mito disease diagnosis

Answer 8

• ragged red fibers = diagnostic
• elevated CK
• increased arginine
• cytochrome oxidase staining: no nito fxn when absent

Question 9

Mitochondrial depletion syndrome

Answer 9

• group of mito conditions caused by AR mutations in nuclear genes associated with mtDNA replication
• causes a reduction in mtDNA in affected tissues
• need muscle biopsy to make diagnosis

Question 10

Barth syndrome

Answer 10

• XL
• neutopenia
• DCM
• 3-methylglutaconic acid in blood and urine

Question 11

Barth syndrome

Answer 11

• XL mutations in TAZ
• neutopenia
• DCM
• elevated 3-methylglutaconic acid in blood and urine
• muscle weakness

Question 12

MNGIE

Answer 12

• Mitochondrial myopathy, peripheral Neuropathy, GastroIntestinal and Encephalopathy
• AR mutations in TYMP