Clinical and molecular studies in five Brazilian cases of Friedreich ataxia

Schwartz, Ida Vanessa Döederlein; Jardim, Laura Bannach; Puga, Ana Cristina; Cocozza, Sérgio; Leistner, Sandra; Lima, Luciane Cauduro

doi:10.1590/s0004-282x1999000100001

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“…Although there are reports in the literature of atypical cases with GAA expansion repeats, none of our atypical cases had them, ruling out the diagnosis of FA in these patients 9,28 . Therefore, molecular analysis is essential for confirming the diagnosis of FA, not only in typical cases, but especially in atypical ones, contributing to Table 2 -Frequency (%) of some findings of the typical form of Friedreich's ataxia 16,17 according to the literature and the present study (with GAA trinucleotide repeats).…”

Section: Discussioncontrasting

confidence: 58%

Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases

Albano¹,

Zatz²,

Kim³

et al. 2001

Rev. Hosp. Clin.

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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...

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Section: Discussioncontrasting

confidence: 58%