Lecture 5: Mitochondrial Myopathies

Question 1

what does the mitochondrial genome code for

Answer 1

• 13 respiratory chain proteins
• 2 rRNA
• 22 tRNA

Question 2

what are the reactive oxygen species

Answer 2

• superoxide anion
• hydroxyl radical
• peroxide ion
• hydrogen peroxide
• hypochlorous acid

Question 3

example of mitochondrial transport system defect

Answer 3

carnitine palmitoyltransferase deficiency

Question 4

example of substrate utilisation defect

Answer 4

• pyruvate dehydrogenase complex deficiency

- fatty acid oxidation defects

Question 5

example of TCA cycle defects

Answer 5

• fumarase deficiency

- alpha ketoglutarate dehydrogenase deficiency

Question 6

example of OXPHOS coupling defect

Answer 6

Luft’s syndrome

Question 7

example of oxidative phosphorylation defects

Answer 7

complex I, II, III, IV and V (ATP synthase) deficiencies

Question 8

features of mitochondrial myopathies

Answer 8

• group of neuromuscular diseases
• most occur before the age of 20
• often begin with exercise intolerance and muscle weakness
• heart failure
• rhythm disturbance
• dementia
• deafness
• blindness
• seizures

Question 9

what are the mitochondrial myopathies caused by mitochondrial DNA mutations

Answer 9

• Lebers Hereditary Optic Neuropathy (LHON)
• Myoclonus Epilepsy with Ragged-Red Fibre (MERRF)
• Mitochondrial Encephelomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS)
• Kearns-Sayre Syndrome (KSS)

Question 10

what happens in LHON syndrome

Answer 10

• mitochondria are partially defective in electron transport
• causes optic nerve damage and blindness

Question 11

what happens in MERRF syndrome

Answer 11

• disrupts synthesis of proteins essential for oxidative phosphorylation
• skeletal muscle fibres of MERRF patients have abnormally shaped mitochondria: ragged red fibres

Question 12

what happens in MELAS syndrome

Answer 12

• primarily affects the brain and skeletal muscle
• causes mitochondrial encephalomyopathy
  symptoms appear in childhood

Question 13

what are symptoms of MELAS syndrome

Answer 13

• lactic acidosis
• stroke like episodes with muscle weakness
• seizures leading to loss of vision
• movement difficulties
• dementia

Question 14

what happens in KSS

Answer 14

• a 5 kilo base pair deletion

- onset before age 20

Question 15

what are symptoms of KSS

Answer 15

• short stature
• multiple endocrinopathies eg diabetes
• dementia
• retinitis pigmentosa
• lactic acidosis
• elevated cerebrospinal fluid protein content
• cardiovascular issues