title: Atypical Friedreich ataxia in patients with FXN p.R165P point mutation or comorbid hemochromatosis.
abstract: BACKGROUND
  Compound heterozygosity for a trinucleotide repeat expansion and a point mutation in the FXN gene is a rare cause of Friedreich ataxia (FRDA).
  
  
  METHODS
  We identified three Swedish FRDA patients with an FXN p.R165P missense mutation and compared their clinical features with six homozygote trinucleotide repeat expansion carriers. Patients were assessed clinically. Trinucleotide expansion length was determined and lymphocyte frataxin levels measured.
  
  
  RESULTS
  p.R165P mutation carriers became wheelchair bound early, but had retained reflexes, better arm function, milder dysarthria, and were more independent in activities of daily living. One p.R165P mutation carrier developed psychosis. Frataxin levels were higher than in homozygous trinucleotide expansion patients. One patient with homozygous trinucleotide repeat expansions and comorbid hemochromatosis had more severe FRDA symptoms than his sibling without hemochromatosis.
  
  
  CONCLUSIONS
  p.R165P patients progress to a less disabling disease state than typical FRDA. Comorbid hemochromatosis may worsen FRDA symptoms through additive effects on iron metabolism.
authors.affiliation: Department of Neurology, Skåne University Hospital, Lund, Sweden; Department of Neurology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Emil
authors.initials: E
authors.lastname: Ygland
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Disease, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Disease, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Disease, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Caldarazzo
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Duno
authors.affiliation: Department of Clinical Genetics, Skåne University Hospital, University and Regional Laboratories, Lund University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Soller
authors.affiliation: Department of Neurology, Skåne University Hospital, Lund, Sweden; Department of Neurology, Clinical Sciences, Lund University, Lund, Sweden. Electronic address: Andreas.Puschmann@med.lu.se.
authors.forename: Andreas
authors.initials: A
authors.lastname: Puschmann
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005621:Friedreich Ataxia / Q000150:complications / Q000235:genetics*; D006432:Hemochromatosis / Q000150:complications*; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics*; D017354:Point Mutation; D019680:Trinucleotide Repeat Expansion; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin
keywords: Disease progression; Friedreich ataxia; Genetic counseling; Hemochromatosis; Point mutation