Atypical Friedreich ataxia in patients with FXN p.R165P point mutation or comorbid hemochromatosis |
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| Institution: | 1. Department of Biological Chemistry and Institute of Biochemistry and Biophysics (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956,C1113AAD Buenos Aires, Argentina;2. Bioinformatics Unit, Fundación Instituto Leloir, Av. Patricias Argentinas 435, Buenos Aires, Argentina;3. Department of Biology, University of Padova, Viale G. Colombo 3, 35131 Padova, Italy;1. Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Japan;2. Second Department of Internal Medicine, University of Toyama, Japan;3. Department of Pathology, Graduate School of Medicine, University of Tokyo, Japan;4. Department of Neurology, Graduate School of Medicine, University of Tokyo, Japan;5. Department of Pathology, Mitsui Memorial Hospital, Japan;6. Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, Japan |
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| Abstract: | BackgroundCompound heterozygosity for a trinucleotide repeat expansion and a point mutation in the FXN gene is a rare cause of Friedreich ataxia (FRDA).MethodsWe 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.Resultsp.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.Conclusionp.R165P patients progress to a less disabling disease state than typical FRDA. Comorbid hemochromatosis may worsen FRDA symptoms through additive effects on iron metabolism. |
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| Keywords: | Friedreich ataxia Point mutation Disease progression Hemochromatosis Genetic counseling |
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