Compound Heterozygote Friedreich Ataxia Patients With Covert Proximal FXN Gene Deletions

We present Friedreich ataxia patients with frataxin gene deletions. Data and records were collected at the Children's Hospital of Philadelphia from patients enrolled in the FACOMS natural history study. Patients with proximal deletions initially diagnosed with only one GAA expanded allele had more severe disease than their homozygous expansion counterparts, including increased frequency of cardiomyopathy, diabetes, and optic neuropathy. Their phenotypes were like those of individuals with distal deletions and null pathogenic variants in the frataxin gene. Covert proximal frataxin gene deletions should be suspected when genetic testing fails to demonstrate two distinct expanded alleles in patients with severe phenotypes.