Background. The most frequent manifestation of mitochondrial DNA (mtDNA) mutation 8344 A ® G is MERRF
syndrome (Myoclonic Epilepsy and Myopathy with Ragged Red Fibres). Less frequent symptoms include ataxia,
perceptive type of deafness, cardiomyopathy or external ophthalmoplegia and mental and motor retardation in
children. We describe heterogeneity of clinical symptoms and results of biochemical and molecular investigations
in four families with the heteroplasmic mutation 8344 A ® G in mtDNA.
Methods and Results. In co-operation with paediatric, neurological and genetic specialists from the Czech and
Slovak Republic we found in 1993 - 1998 at the enzymatic or molecular level more than 90 children and adults with
impaired mitochondrial energy metabolism. Heteroplasmic mutation 8344 A ® G in mtDNA was found in four
families. Ataxia and progressive muscle weakness appeared in the first proband with 50% of mutated copies of
mtDNA in muscle at the age of 30 years. The second proband with 95% of mutated mtDNA had his first clinical
symptoms - muscle hypotonia, cardiomyopathy and mental and motor retardation - in infancy while his four relatives
with 25 - 50% mutated mtDNA lack so far clinical symptoms. In a female from the third family with 50% mutated
mtDNA in muscle the disease manifested at the age of 42 years with progressive external ophthalmoplegia (PEO)
and muscle weakness. In the fourth proband with 50% of mutated mtDNA in blood the disease started in infancy
with spastic quadruparesis and arrested mental and motor development. Enzymatic and histochemical investigation
in muscle biopsy in two probands revealed lower cytochrom c oxidase activity. Ragged-red fibres were found only
in one adult patient.
Conclusions. MtDNA mutation 8344 A ® G can manifest by heterogeneous symptoms. A higher percentage of
mutated mtDNA is usually associated with more serious forms of the disease, but there is not always a correlation
between the degree of heteroplasmy and severity of the disease or the age of the first clinical symptoms.
MERRF syndrome, mtDNA, mutation 8344 A ® G, cytochrome c oxidase, clinical heterogeneity.