Neuro-Ophthalmological Findings in Friedreich’s Ataxia

Abstract

Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by a severe autosomal recessive genetic disorder of the central nervous (CNS) and peripheral nervous system (PNS), affecting children and young adults. Its onset is before 25 years of age, with mean ages of onset and death between 11 and 38 years, respectively. The incidence is 1 in 30,000–50,000 persons. It is caused, in 97% of cases, by a homozygous guanine-adenine-adenine (GAA) trinucleotide mutation in the first intron of the frataxin (FXN) gene on chromosome 9 (9q13–q1.1). The mutation of this gene causes a deficiency of frataxin, which induces an altered inflow of iron into the mitochondria, increasing the nervous system’s vulnerability to oxidative stress. The main clinical signs include spinocerebellar ataxia with sensory loss and disappearance of deep tendon reflexes, cerebellar dysarthria, cardiomyopathy, and scoliosis. Diabetes, hearing loss, and pes cavus may also occur, and although most patients with FRDA do not present with symptomatic visual impairment, 73% present with clinical neuro-ophthalmological alterations such as optic atrophy and altered eye movement, among others. This review provides a brief overview of the main aspects of FRDA and then focuses on the ocular involvement of this pathology and the possible use of retinal biomarkers.

Impacts of impaired mitochondrial dynamics in hearing loss: Potential therapeutic targets

“…In addition to the above-mentioned genes involved in the regulation of mitochondrial dynamics, which can lead to hearing loss in humans and animals, the mitochondrial dynamics mechanism is also involved in the occurrence of some hereditary hearing loss. Friedreich’s ataxia (FRDA) is a hereditary neurodegenerative disease caused by mutations in the frataxin ( FXN ) gene encoding the protein frataxin, and sensorineural hearing loss is one of the clinical symptoms of this disease ( Rojas et al, 2021 ). Frataxin is located in mitochondria and plays a key role in the maintenance of mitochondrial function and iron metabolism balance.…”

Retinal and Visual Pathways Involvement in Carriers of Friedreich’s Ataxia

“…At the present, there is a lack of similar studies on C-FRDA, and our novel findings cannot be supported or contrasted by the available literature. Our ophthalmological data can be considered only in light of everything previously reported in FDRA disease referring exclusively to affected patients with or without visual symptoms (see Introduction [ 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 39 ].…”

“…In overt FRDA disease, two-thirds of patients may display visual system impairment [ 7 ], ocular motor abnormalities being the most frequent and therefore well characterized in this neurological disorder [ 7 ]. Indeed, saccadic dysmetria, frequent square wave jerks [ 8 ], disruption of tracking movements, and impaired visual–vestibular interaction [ 9 ] have been reported, reflecting the disruption of the brainstem, cortical, and vestibular pathways.…”

“…Indeed, saccadic dysmetria, frequent square wave jerks [ 8 ], disruption of tracking movements, and impaired visual–vestibular interaction [ 9 ] have been reported, reflecting the disruption of the brainstem, cortical, and vestibular pathways. Other ophthalmological manifestations can be found in up to 30% of patients [ 7 , 10 , 11 ], including optic neuropathy and, less commonly, peripheral retinopathy [ 1 , 12 ] or pattern dystrophy [ 13 ].…”

“…Optic nerve dysfunction detected by VEP associated with optic nerve pallor [ 11 , 14 , 15 ], as well as reduced RGC function observed by PERG, suggested a neurodegenerative process involving both optic nerve and inner retina in FRDA [ 14 ]. In addition, the morphological analysis by means of OCT of both the optic nerve and macular region showed a reduced thickness of the retinal nerve peripapillary fiber layers (RNFL) [ 7 , 12 , 16 ] of the RGC and of the macular layers, altogether considered signs of neurodegenerative processes [ 7 , 10 , 16 , 17 ].…”