Introduction: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes.Methods: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia -19 typical and 6 atypical -using a long-range PCR test.Results: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) -all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions.Discussion: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion. DESCRIPTORS: Friedreich's ataxia. Trinucleotide expansion repeats. GAA expansion.Friedreich's ataxia (FA) (OMIM 277460) 23 , a neurodegenerative disorder, is the most frequent form of hereditary ataxia, with a prevalence of 1:50,000. Clinical diagnostic criteria for typical cases basically include: a) early age of onset < 20 16 or 25 years 17 , b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. Chamberlain et al. (1988) 8 mapped the Friedreich's ataxia gene to chromosome 9, which was subsequently confirmed 15 . Later, recombinant events 3 allowed the successive narrowing of the candidate region 7,10,22,26 . Campuzano et al. (1996) 6 detected in about 96% of Friedreich's ataxia patients an expanded GAA (guanine, adenine, and adenine) trinucleotide repeat in intron 1 of the gene X25 (with 7 exons-1 to 5a, 5b, and 6-spanning 95 kb of genomic DNA) that encodes a 210-amino acid protein, frataxin, whose function is unknown. Absence of deep tendon reflexes in lower limbs has been included in the diagnostic criteria both by the Geoffroy et al. (1976) and Harding (1981) 16,17 ; however, clinical variability has been reported 11,14 , especially related to the 144 REV. HOSP. CLÍN. FAC. MED. S. PAULO 56(5): [143][144][145][146][147][148] 2001 SEPTEMBER-OCT...