Maternally inherited, affecting the most energy dependent tissues
Expansion
Inheritance is maternal only, because mitochondria come from the ovum. An affected father cannot transmit it, and an affected mother transmits to all her children, though severity varies.
Heteroplasmy explains that variability: cells contain a mixture of normal and mutant mitochondrial DNA, and disease appears only above a threshold proportion. That proportion differs between tissues and between siblings, which is why the same mutation can cause very different phenotypes.
The tissues affected are the most energy dependent: brain, muscle, heart, retina, cochlea, endocrine pancreas and renal tubule. Hence the frequent combination of myopathy, encephalopathy, deafness, diabetes and cardiomyopathy in one patient.
Named syndromes
- MELAS - Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, in a non-vascular distribution
- MERRF - Myoclonic Epilepsy with Ragged Red Fibres
- Leber’s hereditary optic neuropathy - painless bilateral central visual loss in young men
- Kearns-Sayre - progressive external ophthalmoplegia, retinitis pigmentosa, heart block
- Maternally inherited diabetes and deafness
Clues to suspect it: a raised lactate, multisystem disease not fitting one organ, a maternal family history, and ragged red fibres on muscle biopsy with Gomori trichrome staining.
Caution: valproate is hazardous in mitochondrial disease, particularly POLG mutations, where it can precipitate fatal liver failure.