Abstract
BackgroundFriedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition which also has effects on the heart. In 96% of affected individuals FRDA is due to homozygosity of a GAA repeat expansion in intron 1 of the frataxin (FXN) gene. The number of GAA repeats have been shown to relate to disease severity in FRDA, this thought to be via an inverse relationship of GAA repeat number and cellular frataxin levels. We investigated the effects of FRDA on regional long axis function of the left and right ventricles, and also the relationship of long axis systolic (s`) and early diastolic (e`) peak velocities with GAA repeat number on the shorter (GAA1) and longer FXN alleles (GAA2).MethodsThe study group of 78 adult subjects (age 32±9 years) with FRDA and normal left ventricular (LV) ejection fraction were compared to 54 healthy control subjects of similar age, sex and body size. Tissue Doppler imaging (TDI) signals were recorded at the mitral annulus for measurement of s`and e`of the septal, lateral, anterior and inferior walls and at the tricuspid annulus for measurement of right ventricular (RV) s`and e`.ResultsAll the regional LV s`and e`, and both RV s`and RV e`, were lower in individuals with FRDA compared to controls (p<0.001 for all). On multivariate analysis, which included LV septal wall thickness (SWT), RV s`and RV e`were both inversely correlated with GAA1 (β = -0.32 & -0.33, respectively, p = 0.01), but not with GAA2, whereas anterior and lateral s`were both inversely correlated with GAA2 (β = -0.25 and β = -0.28, p = 0.02) but not with GAA1. Increasing SWT was the most consistent LV structural correlate of lower s`and e`, whereas age was a consistent inverse correlate of e`but not of s`.ConclusionThere are generalized abnormalities of both LV regional and RV long axis function in FRDA, but there are also regional differences in the association of this dysfunction with the smaller and larger GAA repeats in the FXN gene.
Highlights
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition due to a deficiency in the mitochondrial protein frataxin (FXN), and in 96% of affected individuals it is due to homozygosity of a GAA repeat expansion in intron 1 of the FXN gene [1]
All the regional Left ventricular (LV) s‘and e‘, and both right ventricular (RV) s‘and RV e‘, were lower in individuals with FRDA compared to controls (p
Left ventricular (LV) structural involvement prior to both cardiac symptom onset and reduction in LV ejection fraction in FRDA has been documented in a number of studies, with increases in LV wall thickness, reduction in LV chamber size and an increase in LV relative wall thickness (RWT), being commonly reported findings [4,5]
Summary
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition which has effects on the heart. In 96% of affected individuals FRDA is due to homozygosity of a GAA repeat expansion in intron 1 of the frataxin (FXN) gene. The number of GAA repeats have been shown to relate to disease severity in FRDA, this thought to be via an inverse relationship of GAA repeat number and cellular frataxin levels. We investigated the effects of FRDA on regional long axis function of the left and right ventricles, and the relationship of long axis systolic (s‘) and early diastolic (e‘) peak velocities with GAA repeat number on the shorter (GAA1) and longer FXN alleles (GAA2)
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