Mitochondrial Diseases

• Mitochondria – primary role in oxidative phosphorylation
• Small amount of DNA – 16kb
• 22 tRNAs
• 2 rRNA
• 13 proteins
• Maternally inherited
• (Only one or two isolated reports of paternal inheritance)
• Randomly segregated at cell division so a random proportion of the oocytes are affected and not all mitochondria in the oocyte are affected resulting in heterogenous expression

• Prevalence of mitochondrial diseases:
• ~12-16 /100,000
• Mechanisms of mutations:
• Point mutations
• MELAS, MERRF, NARP, MILS, LHON
• DNA deletions
• CPEO, KS

MELAS

Diagnosis

CSF

•   Lactate

In one study (in MELAS and Leigh syndrome children) both blood and CSF lactate higher than controls

o Blood avg 4.62mmol/L (41.6 mg/dl) (vs control 1.62mmol/L (14.6mg/dl))

o CSF avg 4.94mmol/L (44.5mg/dl) (vs control 1.42mmol/L (12.8mg/dl))

o Ratio lactate CSF/blood 1.5 (vs 0.5)

· (Diagnostic accuracy of blood and CSF lactate in identifying children with mitochondrial diseases affecting the central nervous system,  Yamada K,  Brain and Development 2012 vol: 34 (2) pp: 92-97)

CSF

Pyruvate (from Yamada et al 2012)

· Blood avg

	Mito (umol/L)	Control
Blood	284	136
CSF	261	90
Ratio CSF/blood	0.9	0.66