Correlation Between the SARA and A-T NEST Clinical Severity Scores in Adults with Ataxia-Telangiectasia.

Ataxia-Telangiectasia (A-T) is an autosomal recessive neurodegenerative disease associated with cerebellar ataxia and extrapyramidal features. A-T has a complex and diverse phenotype with varying rates of disease progression. The development of robust natural history studies and therapeutic trials relies on the accurate recording of phenotype using relevant and validated severity of illness indexes. We compared the commonly used Scale for the Assessment and Rating of Ataxia (SARA) and the disease-specific A-T Neurological Examination Scale Toolkit (A-T NEST), in our adult A-T cohort. We found a strong correlation between A-T NEST and the established SARA score, validating the use of A-T NEST and SARA in capturing the natural history of A-T patients.

Case report: Mutations in DNAJC30 causing autosomal recessive Leber hereditary optic neuropathy are common amongst Eastern European individuals.

Background: Leber Hereditary Optic Neuropathy (LHON) is the most common inherited mitochondrial disease characterized by bilateral, painless, subacute visual loss with a peak age of onset in the second to third decade. Historically, LHON was thought to be exclusively maternally inherited due to mutations in mitochondrial DNA (mtDNA); however, recent studies have identified an autosomal recessive form of LHON (arLHON) caused by point mutations in the nuclear gene, DNAJC30. Case Presentations: In this study, we report the cases of three Eastern European individuals presenting with bilateral painless visual loss, one of whom was also exhibiting motor symptoms. After a several-year-long diagnostic journey, all three patients were found to carry the homozygous c.152A>G (p.Tyr51Cys) mutation in DNAJC30. This has been identified as the most common arLHON pathogenic variant and has been shown to exhibit a significant founder effect amongst Eastern European individuals. Conclusion: This finding adds to the growing cohort of patients with arLHON and demonstrates the importance of DNAJC30 screening in patients with molecularly undiagnosed LHON, particularly in Eastern European individuals. It is of heightened translational significance as patients diagnosed with arLHON exhibit a better prognosis and response to therapeutic treatment with the co-enzyme Q10 analog idebenone.