Objective: To evaluate longitudinal neurological disease progression in the largest available worldwide cohort of adults with ataxia-telangiectasia.

Background: Ataxia-telangiectasia (AT) is a rare, multisystem neurodegenerative disorder with marked clinical heterogeneity. Longitudinal data on neurological progression remain limited, restricting understanding of disease mechanisms and therapeutic trial design.

Method: We analysed longitudinal Scale for the Assessment and Rating of Ataxia (SARA) data from the largest published adult AT cohort to date (n=82, age >16 years). Linear mixed-effects models were used to estimate baseline severity at the time of diagnosis and annual progression rates in classic and variant AT, and to examine clinical and genetic modifiers.

Results: Neurological impairment progressed with a mean SARA increase of 0.38 points per year. Adults with classic AT were more severely than those with variant AT, with SARA scores approximately 9–10 points higher. However neurological progression in adulthood was similar between classic and variant AT (0.33 vs 0.41 points/year), including 15 individuals with the antisense oligonucleotide targetable c.5763-1050A>G variant.

Conclusion: Although AT subtypes differ substantially in childhood and adolescence, neurological decline converges to a similar pace in adulthood, irrespective of subtype or genotype. SARA remains a useful outcome measure but may underestimate progression in advanced disease and non-cerebellar domains. These findings inform counselling, prognostication, and the design of interventional trials, including mutation-specific therapies

Longitudinal SARA trajectories per participant

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neurological-disease-progression-in-adults-with-ataxia-telangiectasia-a-longitudinal-study/