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Comorbidities in Friedreich ataxia: incidence and manifestations from early to advanced disease stages

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Abstract

Objectives

Friedreich’s ataxia (FA) is the most common hereditary ataxia, characterized by multisystemic manifestations including neurological, cardiological, and skeletal abnormalities. In this study, we aimed to analyze the incidences of disease-related and unrelated comorbidities occurring in different stages of the disease progression.

Methods

We analyzed longitudinal data from a 10-year prospective observational study in a cohort of 175 FA patients with disease onset < 25 years. We analyzed the time of diagnosis for the most frequently reported medical conditions, with respect to age and disease duration of each patient.

Results

In the early stage of the disease, scoliosis (53.3%), hypertrophic cardiomyopathy (46.7%), and pes cavus (33.3%) were the most frequently diagnosed conditions, sometimes occurring even before the onset of ataxia. Diabetes, bone fractures, and depression have the same incidence at all disease stages. In patients with > 20 years of disease duration, the most frequent complications were hearing and visual loss (20% and 26%), arrhythmias (16%), and psychosis (18%). Thirteen patients presented hallucinations/delusions in the absence of neurological acute events or mental illness predisposing to psychotic manifestations. Six of these patients fulfill the diagnostic criteria for Charles Bonnet syndrome.

Conclusions

Incidence of FA-related medical conditions varies according to disease duration. In patients with very long disease duration, we observed an unexpectedly high incidence of visual and auditory pseudo-hallucinations that were not previously reported in FA patients. We hypothesized that these late complications may be possibly related to the severe sensory deafferentation syndrome observed in the advanced stages of FA disease.

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Acknowledgements

L. N., C. G., and C. M. are members of the European Reference Network for Rare Neurological Disorders (ERN-RND), Project ID No. 739510. We are grateful to all patients and family members participating in the study.

Funding

This work was supported by the Italian Ministry of Health, Grant RF-2019–12368918 to CM.

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Authors and Affiliations

  1. Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy

    Mario Fichera, Anna Castaldo, Alessia Mongelli, Gloria Marchini, Cinzia Gellera, Lorenzo Nanetti & Caterina Mariotti

  2. PhD Program in Neuroscience, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    Mario Fichera

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  1. Mario Fichera
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  2. Anna Castaldo
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Correspondence to Lorenzo Nanetti.

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Fichera, M., Castaldo, A., Mongelli, A. et al. Comorbidities in Friedreich ataxia: incidence and manifestations from early to advanced disease stages. Neurol Sci 43, 6831–6838 (2022). https://doi.org/10.1007/s10072-022-06360-w

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