Abstract
Background: Patients with suspected genetic ataxia are often tested for Friedreich's ataxia (FRDA) and/or a variety of spinocerebellar ataxias (SCAs). FRDA can present with atypical, late-onset forms and so may be missed in the diagnostic process. We aimed to determine FRDA-positive subjects among two cohorts of patients referred to a specialist ataxia centre either for FRDA or SCA testing to determine the proportion of FRDA cases missed in the diagnostic screening process.Methods: 2000 SCA-negative ataxia patients, not previously referred for FRDA testing (group A), were tested for FRDA expansions and mutations. This group was compared with 1768 ataxia patients who had been previously referred for FRDA testing (group B) and were therefore more likely to have a typical presentation. The phenotypes of positive cases were assessed through review of the clinical case notes.Results: Three patients (0.2%) in group A had the FRDA expansion on both alleles, compared with 207 patients (11.7%) in group B. The heterozygous carrier rate across both cohorts was of 41 out of 3,768 cases (1.1%). The size of the expansions in the three FRDA-positive cases in group A was small, and their presentation atypical with late-onset.Conclusions: This study demonstrates that FRDA is very rare among patients who were referred purely for SCA testing without the clinical suspicion of FRDA. Such cases should be referred to specialist ataxia centres for more extensive testing to improve patient management and outcomes.
Highlights
Friedreich’s ataxia (FRDA), first described by Nikolaus Friedreich in 1863, is an autosomal recessive disease in which patients develop progressive ataxia involving immobility, lack of manual dexterity, dysarthria, and hypertrophic cardiomyopathy
We present data on FRDA screening of 2000 Spinocerebellar ataxia (SCA)-negative ataxia patients who had not been previously screened for FRDA
We compared the results from this cohort with those from another cohort of patients who were referred for FRDA by their clinicians, in which many more FRDA cases and more typical presentations of the disease were expected to be found
Summary
Friedreich’s ataxia (FRDA), first described by Nikolaus Friedreich in 1863, is an autosomal recessive disease in which patients develop progressive ataxia involving immobility, lack of manual dexterity, dysarthria, and hypertrophic cardiomyopathy It primarily affects the dorsal root ganglia (DRGs) and cerebellar granule cells [1, 2]. In 1996, the mutation causing this disease was mapped to an intronic locus of the FXN gene on chromosome 9q13, which codes for the frataxin protein, which is pathologically deficient in affected cells in FRDA patients [3]. We aimed to determine FRDA-positive subjects among two cohorts of patients referred to a specialist ataxia centre either for FRDA or SCA testing to determine the proportion of FRDA cases missed in the diagnostic screening process
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