High mitochondrial DNA T8993G mutation (> 90%) without typical features ofLeigh's and NARP syndromes

Neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome and maternally inherited Leigh's syndrome have been associated with T8993G point mutation s in the mitochondrial adenosine triphosphatase 6 gene. Typically, NARP syn drome is characterized by developmental delay, seizures, dementia, retiniti s pigmentosa, ataxia, sensory neuropathy, and proximal weakness. Usually, t here is a correlation between the percentage of mutated mitochondrial DNA a nd clinical severity, and when mutated mitochondrial DNA is > 90%, it is of ten seen with Leigh's syndrome. We now report a family with mitochondrial D NA T8993G mutation in eight living members, five with mutant mitochondrial DNA > 90% and one with 20% mutant mitochondrial DNA. However, their clinica l features include variable combinations of seizures, behavior problems, le arning disability, mental retardation, sensorineural deafness, cerebellar a taxia, and proximal muscle weakness. No retinitis pigmentosa was found in a il eight living members, including a 56-year-old grandmother. Only one dead female relative was diagnosed with Leigh's syndrome on the neuropathologic examination at age 22 years, when she died of an accident, High mitochondr ial DNA T8993G mutation is not always associated with typical features of L eigh's and NARP syndromes.