Mitochondrial Diseases

Question 1

Kearns-Sayre Syndrome (KSS)

• main symptoms
• other features

Answer 1

Deletion syndrome

MAIN SYMPTOMS:
- Progressive external opthalmoplegia
- Onset before age 20
- Pigmentary retinopathy
PLUS 1 of the following:
- CSF protein >1 g/l
- cerebellar ataxia
- heart block

OTHER:

• short stature, growth hormone deficiency
• deafness
• dementia
• myopathy
• diabetes mellitus
• hypoparathyroidism

Question 2

Pearson syndrome

Answer 2

DNA deletion syndromes

Sideroblastic anemia
Pancreatic insufficiency

Question 3

Progressive external Opthalmoplegia

Answer 3

May be associated with KSS or isolated

PEO is ptosis and weakness of extraocular muscle

Can also have proximal limb weakness

Question 4

Leber Hereditary Optic Neuropathy (LHON)

Answer 4

Mitochondrial DNA point mutation syndrome

Bilateral painless sub acute visual failure
Usually in young adults
Male>female
3 most common muts account for 90% of cases
Usually homoplasmic mutations

Question 5

MELAS

Answer 5

Mitochondrial DNA point mutation syndrome

Mitochondrial Encephalomyopathy Lactis acidosis And Stroke-like episodes

mutation: MT-TL1. encodes tRNA Leucine

Question 6

MERRF

Answer 6

Mitochondrial DNA point mutation syndrome

Myoclonic Epilepsy Ragged Red Fibers

ataxia
Muscle biopsy shows ragged red fibers

mutation: MT-TK encodes tRNA lysine

Question 7

Leigh Syndrome

Answer 7

Mitochondrial DNA point mutation syndrome

Progressive neurological disease

Sign and symptoms of basal ganglia and/or brain stem disease
Characteristic neuroimaging/neuropathology
Raised lactate

Can be caused by mitochondrial gene of nuclear gene
- autosomal recessive or X-linked

Question 8

NARP

Answer 8

Mitochondrial DNA point mutation syndrome

Neurogenic Ataxia Retinitis Pigmentosa

MT-ATP6 only known gene

Question 9

Mitochondrial disease of nuclear origin

Answer 9

Includes disorders:

• resulting from nuclear encoded structural subunits or assembly factors of the respiratory chain
• of mitochondrial DNA replication or stability
• of DNA depletion
• related to gamma polymerase
• –>PEO
• of mitochondrial translation
• of mitochondrial network dynamics