Background. The most frequent manifestations of heteroplasmic mitochondrial DNA (mtDNA) mutation 8993
T>G are Leigh syndrome or NARP syndrome (Neurogenic Muscle Weakness, Ataxia, and Retinitis Pigmentosa).
The authors describe heterogeneity of clinical symptoms and results of biochemical and molecular analyses in seven
severely clinically affected children from two unrelated families with heteroplasmic mtDNA mutation 8993 T>G.
Methods and Results. Seven clinically affected children from two unrelated families were born in term after an
uneventful pregnancy. The failure to thrive, psychomotor retardation, hypotonic or spastic quadruparesis, hypertrophic
cardiomyopathy, hepatopathy and hyperlactacidaemia developed after birth. Five children died in the first year
of life during acute respiratory infection, one girl died at the age of 3 months with sudden death syndrome, only one
boy with spastic quadruparesis and severe psychomotor retardation survived to the age of 8 years.Molecular analyses
in all investigated children and their clinically non-affected mothers revealed the presence of heteroplasmic mtDNA
mutation 8993 T>G. Mutated copies of mtDNA molecules in maternal tissues were in the range of 15–22 %. The
mutation load in all analysed children’s tissues was higher than 90 %.
Conclusions. A broad spectrum of clinical symptoms may be observed in families with heteroplasmic mtDNA
mutations 8993 T>G. Affected children with a mutation load higher than 90 % usually do not survive after infancy.
In both investigated families, a profound increase in the levels of heteroplasmy of mtDNA mutation 8993 T>G was
observed in two subsequent generations.
NARP syndrome, Leigh syndrome, mtDNA mutation 8993 T>G, heteroplasmy, lactate acidosis.