Objective: We aimed to investigate patients with hereditary ataxias (HA) and spastic paraplegias (HSP) followed in our hospital and to evaluate the percentage of patients that achieved a genetic diagnosis taking into account the type of molecular method and the economic cost.

Background: HA and HSP are a group of clinically and genetically heterogeneous neurodegenerative disorders. Despite advances in molecular research, molecular diagnosis is very challenging.

Method: We conducted a descriptive cross-sectional study of patients with confirmed or suspected HA and HSP followed in our hospital between 2009 and 2021. Demographic, clinical, neuroimaging and genetic data were collected.

Results: We identified 59 patients of 56 families followed in our hospital: 46 had HA, 9 HSP and 4 a combination of HA and HSP. There were 27 women (45.8%), mean age at genetic testing was 58 years (range 18-85) and mean age of onset was 44 years (range 2-78). 23(39%) patients had positive family history, 22(37.2%) pyramidal signs, 13(22%) peripheral neuropathy and 29(49.1%) cerebellar atrophy. Molecular diagnosis was achieved in 13(22%) patients: Friedreich’s ataxia was diagnosed in 5, SCA3 in 2 and the rest in only one patient: SCA7, SPG15, SPG26, SPG48, POLR3A-related spastic ataxia and episodic ataxia type 2. The molecular diagnostic methods were: single-gene tests including repeat primed PCR and Sanger sequencing (8 out of 45 patients achieved diagnosis); gene panel (1 out of 3 patients achieved diagnosis); and whole exome sequencing (4 out of 8 patients achieved diagnosis). The mean cost per patient of all molecular diagnoses excluding gene panels and exome sequencing was 686.44 euros. In 8(13%) patients the cost was superior to the cost of an exome sequencing.

Conclusion: We found a high percentage of genetically undiagnosed patients despite genetic tests performed. In our patients, the whole exome sequencing achieved a higher diagnostic rate.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/challenges-in-diagnosis-of-hereditary-ataxia-and-spastic-paraplegias/