Objective: Our objective was to validate “RADIAL” ( Recessive Ataxias ranking differential DIagnosis Algorithm) for the diagnosis of Autosomal Recessive Cerebellar Ataxia (ARCA).

Background: ARCA is a complex and heterogenic group of rare disorders (1). The next generation sequencing (NGS) open new diagnostic perspectives but we lack tools to help their interpretation. RADIAL has been produced based on literature of 67 ARCAs and expert opinion. 124 clinical and paraclinical features were described for each of these entities. The relationship between each feature and entity was defined by frequency and specificity. The phenotype of a patient suspected with ARCA is automatically compared to the phenotype of all 67 entities, leading to a score for each entity according to the match between the phenotype and each entity. The higher the score, the more probable the entity. RADIAL was initially evaluated on a retrospective cohort of 864 patients where the top 3 highest-scores had an average sensitivity and specificity of 92.2% and 95.4%, respectively (2).

Method: We propose a prospective validation of RADIAL in a cohort of consecutive patients with ARCA referred to our center. For each patient, the top 3 highest-scoring diagnoses proposed by RADIAL were compared to the results of NGS (Friedreich ataxia diagnosis and panel of 312 genes responsible for cerebellar ataxia and/or movement disorders).

Results: Thirteen patients with ARCA have been at this stage included. Genetic studies found 3 ataxia with oculomotor Apraxia type 2, 2 ataxia with vitamin E deficiency, 1 SPG7, 3 Friedreich ataxia, 1 cerebrotendinous xanthomatosis, 1 Niemann Pick type C and 1 ARCA type 3. RADIAL provided the correct diagnosis with the highest score of probability for 10/13 cases, for 2 of the 3 others, the correct diagnosis was proposed in the top 3.

Conclusion: These preliminary results confirm that RADIAL is an efficient algorithm, easy and quick to use in clinical practice. The aim of this tool is to improve the diagnosis approach in front of ARCA and to help the clinicians to interpret the mass of data allowed by the NGS.

References: 1. Anheim M, Tranchant C, Koenig M. The autosomal recessive cerebellar ataxias. N Engl J Med 2012. 2. Renaud. M, Tranchant C, Martin JVT et al, A recessive ataxia diagnosis algorithm for the next generation sequencing era. Ann Neurol. Epub 2017 Nov 21

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MDS Abstracts - https://www.mdsabstracts.org/abstract/assessment-of-radial-a-tool-for-the-diagnostic-of-autosomal-recessive-cerebellar-ataxia-a-prospective-study/