NARP and mitochondrial DNA associated Leigh syndrome are part of a continuum of progressive neurodegenerative disorders among those affected within the same family. The most common mutations are 8993T>G and 8993T>C mutations in the MTATP6 gene. The clinical phenotype is typically more severe with the 8993T>G mutation than the 8993T>C mutation. Usually a Leigh disease presentation is observed in patients with mutant heteroplasmy greater than 90%. Patients carrying approximately 75-90% mutant load may have NARP syndrome, and between 60-75% may exhibit only retinitis pigmentosa. Approximately 10-20% of individuals with Leigh disease have either the 8993T>G or 8993T>C mutation. Due to genetic and clinical heterogeneity and multisystem dysfunction, we highly recommend the mitochondrial DNA screening panel (see Mitochondrial DNA Screen (Point Mutations and Deletions)) for a patient suspected of NARP or Leigh disease, unless a specific mutation has already been detected in the family. Reasons for Referral:
Testing Methodology:Please refer to Mitochondrial DNA Screen (Point Mutations and Deletions) |