Friedreich ataxia in Norway – an epidemiological, molecular and clinical study

Orphanet Journal of Rare Diseases

Chantal ME Tallaksen¹  Tone Berge³  Per Morten Knappskog²  Torunn Fiskerstrand²  Kaja Kristine Selmer¹  Sandra Pilar Henriksen³  Mette Kroken⁴  Iselin Marie Wedding³ 

[1] University of Oslo, Faculty of Medicine, Oslo, Norway;Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway;Department of Neurology, Oslo University Hospital, Ullevaal 0407, Oslo, Norway;Department of Medical Genetics, Oslo University Hospital, Ullevaal 0407, Oslo, Norway

关键词: Norway;    Autosomal recessive;    Ataxia;    Frataxin;    FRDA;    Friedreich ataxia;   

Others  :  1224096
DOI  :  10.1186/s13023-015-0328-4

 received in 2015-07-06, accepted in 2015-08-25,  发布年份 2015

【 摘 要 】

Background

Friedreich ataxia is an autosomal recessive hereditary spinocerebellar disorder, characterized by progressive limb and gait ataxia due to proprioceptive loss, often complicated by cardiomyopathy, diabetes and skeletal deformities. Friedreich ataxia is the most common hereditary ataxia, with a reported prevalence of 1:20 000 – 1:50 000 in Central Europe. Previous reports from south Norway have found a prevalence varying from 1:100 000 – 1:1 350 000; no studies are previously done in the rest of the country.

Methods

In this cross-sectional study, Friedreich ataxia patients were identified through colleagues in neurological, pediatric and genetic departments, hospital archives searches, patients’ associations, and National Centre for Rare Disorders. All included patients, carriers and controls were investigated clinically and molecularly with genotype characterization including size determination of GAA repeat expansions and frataxin measurements. 1376 healthy blood donors were tested for GAA repeat expansion for carrier frequency analysis.

Results

Twenty-nine Friedreich ataxia patients were identified in Norway, of which 23 were ethnic Norwegian, corresponding to a prevalence of 1:176 000 and 1:191 000, respectively. The highest prevalence was seen in the north. Carrier frequency of 1:196 (95 % CI = [1:752–1:112]) was found. Homozygous GAA repeat expansions in the FXN gene were found in 27/29, while two patients were compound heterozygous with c.467 T < C, L157P and the deletion (g.120032_122808del) including exon 5a. Two additional patients were heterozygous for GAA repeat expansions only. Significant differences in the level of frataxin were found between the included patients (N = 27), carriers (N = 37) and controls (N = 27).

Conclusions

In this first thorough study of a complete national cohort of Friedreich ataxia patients, and first nation-wide study of Friedreich ataxia in Norway, the prevalence of Friedreich ataxia in Norway is lower than in Central Europe, but higher than in the last Norwegian report, and as expected from migration studies. A south–north prevalence gradient is present. Based on Hardy Weinberg’s equilibrium, the carrier frequency of 1:196 is consistent with the observed prevalence. All genotypes, and typical and atypical phenotypes were present in the Norwegian population. The patients were phenotypically similar to European cohorts. Frataxin was useful in the diagnostic work-up of heterozygous symptomatic cases.

【 授权许可】

   
2015 Wedding et al.

【 图 表 】

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