Abstract

Progressive signs of ataxia in a eight year old girl with hypo-active knee and ankle jerks, prompted the analysis of the frataxin gene (FXN; 606829). The most common molecular abnormality - GAA trinucleotide repeat expansion in intron 1 - was found with +300 GAA repeats (1490bp) (normal individuals have 5 to 30 GAA repeats expansions, whereas affected individuals have from 70 to more than 1,000 GAA triplets). Additionally she had unstable gait with incoordination of limb movements, impairment of position and vibratory senses, dysarthria, pes cavus, positive Babinski sign and scoliosis. At the age of fourteen the girl was referred in a comatose condition, in severe diabetic ketoacidosis. Insulin dependent diabetes mellitus was since treated with insulin preparations. Electrocardiogram showed diffuse T wave inversion with sinus bradycardia, while ultrasound revealed concentric, symmetric hypertrophy of the left ventricle leading to the diagnosis of hypertrophic cardiomyopathy. At the age of 14, she is bound to the wheel-chair, unable to walk. Her brother started to show ataxia at the age of 8 years and subsequent analysis also showed hypertrophic cardiomyopathy. His mutational analysis revealed the same frataxin abnormality with +300 GAA repeats. So far, no signs of diabetes occurred. The parental DNA was not available for analysis.

Key words: Friedreich’s ataxia, diabetes mellitus type 1, hypertrophic cardiomyopathy, siblings