MERRF (myoclonic epilepsy with ragged-red fibres)
A maternally inherited mitochondrial disease of myoclonic jerks, seizures, unsteadiness and muscle weakness.
What it is
A mitochondrial DNA disorder, most often caused by the m.8344A>G variant in MT-TK, the mitochondrial transfer RNA for lysine.
See it in 3D
Who gets it
Rare; estimated at a few per 100 000 people.
Causes
- The m.8344A>G variant in MT-TK in about 80 % of cases; other MT-TK variants in a few
- Maternal (mitochondrial) inheritance with heteroplasmy
Pathophysiology
The faulty transfer RNA impairs translation of all 13 mtDNA-encoded respiratory-chain proteins, so oxidative phosphorylation fails in tissues with high energy needs once the mutant load passes their threshold. Abnormal mitochondria accumulate under the muscle membrane, giving «ragged-red» fibres on biopsy.
Symptoms and signs
- Myoclonus (sudden muscle jerks), often the first sign
- Generalised seizures
- Ataxia
- Muscle weakness and exercise intolerance
- Hearing loss, short stature, optic atrophy, multiple lipomas or cardiomyopathy in some
Diagnosis
- Clinical
- Myoclonus with epilepsy, ataxia and myopathy, especially with similar problems along the maternal line.
- Tests
- High blood and cerebrospinal fluid lactate; mtDNA testing for m.8344A>G in blood, urine or muscle; muscle biopsy showing ragged-red fibres and cytochrome c oxidase-deficient fibres.
- Imaging
- Brain MRI may show cerebellar atrophy.
Treatment
- Medical
- Antiseizure treatment, choosing drugs suitable for mitochondrial disease.
- Rehabilitation
- Physical therapy and hearing aids.
- Follow-up
- Cardiac and audiological follow-up; genetic counselling for maternal relatives.
Complications
- Progressive neurological disability
- Cardiomyopathy and conduction problems
Prognosis
Variable and usually progressive; severity depends largely on the mutant load in each tissue.
Test yourself
Think of the answer, then tap the question to see it.
Which gene and variant cause most cases of MERRF?
m.8344A>G in MT-TK, the mitochondrial transfer RNA for lysine.
What are ragged-red fibres?
Muscle fibres with accumulated abnormal mitochondria beneath the membrane, seen with a special stain on biopsy.
Why do affected relatives of the same mother differ in severity?
Heteroplasmy: they carry different proportions of mutant mtDNA in their tissues.
Connections
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Myoclonic epilepsy with ragged-red fibers: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); MT-TK gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.