CORRELATION BETWEEN LEFT-VENTRICULAR HYPERTROPHY AND GAA TRINUCLEOTIDE REPEAT LENGTH IN FRIEDREICHS-ATAXIA

Background Friedreich's ataxia (FA), the most common inherited ataxia, is associated frequently with cardiac hypertrophy, and death is often cardiac related. Recently, the disease has been associated with a mut ation that consists of an unstable expansion of GAA repeats in the fir st intron of the gene encoding frataxin on chromosome 9. Methods and R esults We studied 44 consecutive patients with FA, determined the size of GAA expansions in the frataxin gene, and examined the relation bet ween the genotype and cardiac phenotype assessed by M-mode and two-dim ensional echocardiography. Ail the patients were homozygous for the mu tation. The size of the GAA expansion on the smaller allele varied fro m 270 to 1200. We found a correlation between the size of GAA expansio n and the left ventricular wall thickness (r=.51, P<.001) and the left ventricular mass index (r=.45, P=.002). Left ventricular hypertrophy was observed in 81% of patients with a number of GAA repeats above the median value of 770 compared with only 14% in the other group (P=.002 ). Conclusions These data demonstrate that in FA, the severity of left ventricular hypertrophy is related to the number of GAA repeats. Thes e results suggest that abnormalities of the gene encoding frataxin, a protein of unknown function highly expressed in the normal heart, may play an important role in the modulation of cardiac hypertrophy.