Whilst most DNA is found in the cell nucleus, a small amount of double-stranded DNA is present in the mitochondria. It encodes protein components of the respiratory chain and some special types of RNA

Mitochondrial inheritance has the following characteristics:

• inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
• none of the children of an affected male will inherit the disease
• all of the children of an affected female will inherit the disease
• generally, encode rare neurological diseases
• poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy

Histology

• muscle biopsy classically shows 'red, ragged fibres' due to increased number of mitochondria

Examples include:

• Leber's optic atrophy
• MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
• MERRF syndrome: myoclonus epilepsy with ragged-red fibres
• Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen
• sensorineural hearing loss

Management

Genomic therapy to avoid maternal transmission:

• Pro-nuclear transfer - transferring a nucleus from a fertilized cell from an affected patient with mitochondrial disease to a fertilized cell from a healthy donor (from which the nucleus has been removed) - the developing embryo will therefore have the mitochondria from a healthy donor.