Objective: To examine the possibility of molecular finding affecting FRDA phenotype, we studied the clinical features and ascertained the GAA repeat sizes in FRDA patients of Indian origin.

Background: Friedreich’s Ataxia (FRDA) is the most common form of hereditary ataxia with features of variable occurrence of cardiomyopathy (60-90%), musculoskeletal deformities (60-80%) and diabetes mellitus (6-32%) is caused by biallelic (GAA trinucleotide repeats) loss of function mutations in FXN.

Method: 94 FRDA patients were recruited with standard neurological evaluation and other paraclinical investigations. GAA-expansion/mutation screening was carried out by Triplet-repeat-primed PCR and expand-long-template PCR protocol.

Results: A total of 94 FRDA patients were shown to have 833 repeats as the median size of the expanded allele (range 200-1233). Cerebellar ataxia, peripheral neuropathy and musculoskeletal deformities were the predominant features observed in >80% of cases. Clinico-genetic findings revealed an inverse correlation between GAA-lower-allele (GAA_LA) and disease age at onset. Dysarthria showed significant dependence on GAA_LA, age, age at onset and duration of the disease. Severity of the FRDA measured using rating scale (FARS) was found to increase with the duration of the disease. Clinical manifestations such as cardiomyopathy and dysarthria had reduced incidence while nystagmus had a higher incidence in our patients in comparison to patients from different populations.

Conclusion: Age at onset has shown a statistically inverse correlation with repeat sizes on lower allele. The molecular genetic testing, which remained mandatory for the FRDA diagnosis and genetic counseling should not be restricted to typical FRDA cases, but should be applied in all cases of autosomal recessive inheritance and early onset sporadic ataxia. Discordance in phenotypes among patients of different population can be attributed to the population genetic background.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-genetic-abnormalities-in-patients-with-friedreichs-ataxia-a-genotype-phenotype-correlation/