Abstract
Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7–15 µg/L), AOA2 (15–65 µg/L) and AT (>65 µg/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.
Highlights
Autosomal recessive cerebellar ataxias (ARCAs) are clinically and genetically heterogeneous disabling inherited neurodegenerative disorders responsible for cerebellar along with other neurological and systemic signs[1]
We report that ataxia with oculomotor apraxia type 1 (AOA1), ataxia with oculomotor apraxia type 2 (AOA2) and ataxia telangiectasia (AT) which together should be considered as a particular group among ARCAs, share many features including complex, overlapping oculomotor disturbances, elevated AFP along with sensorimotor axonal neuropathy, chorea and/or dystonia, cerebellar atrophy and severity
Genuine OMA may be a feature of this group though it is not ubiquitous
Summary
Autosomal recessive cerebellar ataxias (ARCAs) are clinically and genetically heterogeneous disabling inherited neurodegenerative disorders responsible for cerebellar along with other neurological and systemic signs[1]. A group of ARCAs due to DNA repair deficiency, RNA termination or maturation deficiencies, or both, has emerged during the past fifteen years They include ataxia with oculomotor apraxia type 1 (AOA1) due to mutation in APTX2, ataxia with oculomotor apraxia type 2 (AOA2) caused by mutations in SETX3, ataxia telangiectasia (AT) due to mutation in ATM4, and the rarer AT like disorder (ATLD) linked to mutations in MRE11. AOA2 patients develop cerebellar ataxia in the second decade of life, sensorimotor neuropathy, occasional OMA, strabismus, chorea, dystonia and elevated alpha-fetoprotein (AFP) serum levels[8,9,10,11,12]. We compared the clinical, biochemical, video-oculographic, imaging and neurophysiological features of AOA1, AOA2 and AT
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