LATE-ONSET FRIEDREICH ATAXIA - MOLECULAR-GENETICS, CLINICAL NEUROPHYSIOLOGY, AND MAGNETIC-RESONANCE-IMAGING

Objective.-To clarify the nosological classification of late-onset Friedreich's ataxia (LOFA), ie, patients who have later onset of Friedreich's ataxia (FRDA), often after 25 years of age. Design.-Comparison of clinical examination data, nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging of a family with LOFA with a group of patients with FRDA. Genetic linkage analysis was performed in the family with LOFA. Setting.-Referral center. Patients.-Thirteen patients satisfied classic diagnostic criteria of FRDA, and three patients from one family satisfied all diagnostic criteria of FRDA but with disease onset after 25 years. Results.-Results of nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging in patients with LOFA closely corresponded to observations made in patients with FRDA. In addition, genetic linkage analysis using markers tightly linked to the FRDA locus on chromosome 9 showed that all affected members of the LOFA family, but not their unaffected siblings, had inherited identical paternal and maternal genotypes. Conclusion.-Data suggest that LOFA may also result from mutation within the FRDA locus.