1 Klinisk Genetisk Klinik, Juliane Marie Centre, Rigshospitalet, The Capital Region of Denmark2 unknown
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. CONCLUSION: 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.
Parkinsonism and Related Disorders, 2014, Vol 20, Issue 8, p. 919-23