Friedreich's ataxia in patients with FXN p.R165P point mutation

Research output: Contribution to journalPublished meeting abstract


Introduction: Friedreich's ataxia (FRDA) is a hereditary disorder with progressive postural ataxia, dysarthria, neuropathy, muscle weakness and cardiomyopathy. Lack or malfunction of the protein frataxin due to mutations in the frataxin gene (FXN) is the cause of the disease. Most patients are homozygous for GAA trinucleotide expansions in FXN but disease can also be caused by heterozygosity for the expansion and a point mutation. Milder disease has been reported for some FRDA patients with missense mutations. Methods: We describe 3 FRDA patients, not previously reported, with the FXN p.R165P missense mutation and compared clinical features with 6 homozygous GAA expansion carriers. Patients were interviewed, examined clinically and assessed with FRDA rating scale (FARS). Blood was collected for reanalysis of GAA expansion length and for frataxin measurements. Results: Compared to patients homozygous for FXN GAA expansion, p.R165P mutation carriers had more wellpreserved upper limb function and deep tendon reflexes, considerably milder dysarthria, but possibly an increased occurrence of psychosis. p.R165P patients were more independent in activities of daily living, especially when correlated to disease duration. We found no difference in other clinical aspects or in GAA expansion length. One patient had severe FRDA symptoms and comorbid hemochromatosis, whereas his sibling without hemochromatosis had much milder disease. Refined analysis of GAA expansion length and frataxin levels are in progress. Conclusion: p.R165P FRDA patients appear to progress to a less disabling disease state than typical FRDA. We suggest additive effects of comorbid FRDA and hemochromatosis, due to synergistic abnormalities in iron metabolism.


External organisations
  • Skåne University Hospital
  • Carlo Besta Neurological Institute, IRCCS
  • Copenhagen University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology


  • frataxin, trinucleotide, protein, patient, point mutation, human, health care organization, Friedreich ataxia, hemochromatosis, missense mutation, dysarthria, clinical feature, mutation, sibling, disease duration, psychosis, tendon reflex, arm, gene, blood, rating scale, daily life activity, cardiomyopathy, iron metabolism, heterozygosity, muscle weakness, neuropathy, genetic disorder
Original languageEnglish
Pages (from-to)727
Number of pages1
JournalEuropean Journal of Neurology
Issue numberSuppl 1
Publication statusPublished - 2012 Sep 1
Publication categoryResearch
Event16th Congress of the European-Federation-of-Neurological-Societies (EFNS) - Stockholm, SWEDEN
Duration: 2012 Aug 11 → …