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Rapidly progressive multiple system atrophy in a patient carrying LRRK2 G2019S mutation

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Abstract

Background

Multiple system atrophy (MSA) is considered a primarily sporadic neurodegenerative disease, but the role of genetic is poorly understood.

Case

We present a female patient of Moroccan origin who developed a rapidly progressive non-levodopa responsive parkinsonism, gait and balance problems, and dysautonomia including severe bulbar symptoms. She was diagnosed with MSA Parkinsonian-type (MSA-P) and suddenly died at night at 58 years of age. Reduced striatal DAT-SPECT, putaminal hyperintensity on T2-MRI, and hypometabolism with FDG-PET were present. Genetic testing documented a G2019S mutation in the LRRK2 gene. A skin biopsy was obtained and used to perform alpha-synuclein RT-QuIC, which was negative, and immunohistochemical analysis, which demonstrated abnormal alpha-synuclein deposits in cutaneous nerves. Elevated blood neurofilament light chain levels were also documented.

Conclusions

LRRK2 mutations are the most common cause of monogenic Parkinson’s disease (PD) and G2019S is the most frequent variant. Our patient presented with biological, clinical, and radiological features of MSA, but genetic testing revealed a G2019S LRRK2 mutation, which has been previously reported only in one other case of pathologically proven MSA but with mild progression. In our patient, post-mortem confirmation could not be performed, but RT-QuIC and immunohistochemical findings on skin biopsy support the diagnosis of MSA. G2019S LRRK2 may be linked to an increased risk of MSA. Cases of atypical parkinsonism with rapid disease course should be screened for PD-related genes especially in populations with a high prevalence of mutations in known genes.

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Data availability

Data from the patient are available on request.

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Author information

Authors and Affiliations

  1. Parkinson and Movement Disorders Unit, Center for Rare Neurological Diseases (ERN-RND), Study Center On Neurodegeneration (CESNE), Department of Neuroscience, University of Padua, Via Giustiniani 2, 35128, Padua, Italy

    Tommaso Carrer, Giulia Bonato, Michele Sandre, Aron Emmi, Marta Campagnolo, Miryam Carecchio & Angelo Antonini

  2. Department of Medicine (DIMED), University of Padua, Padua, Italy

    Giulia Musso

  3. Department of Biomedical and Neuromotor Sciences (DiBiNeM), University of Bologna, Bologna, Italy

    Piero Parchi

  4. Programma Neuropatologia Delle Malattie Neurodegenerative, Istituto Delle Scienze Neurologiche Di Bologna, IRCCS, Bologna, Italy

    Piero Parchi

Authors
  1. Tommaso Carrer
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  2. Giulia Bonato
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  3. Michele Sandre
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  4. Aron Emmi
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  5. Marta Campagnolo
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  6. Giulia Musso
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  7. Miryam Carecchio
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  8. Piero Parchi
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  9. Angelo Antonini
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Contributions

1. Research project: A. conception, B. organization, C. execution.

2. Manuscript preparation: A. writing of final draft, B. review and critique.

TC: 1A, 1B, 1C, 2A

GB: 1A, 1B, 2A

MS: 1C, 2A

AE: 1C, 2A

GM: 1C

MC: 1A, 2B

PP: 1C, 2B

AA: 1A, 2B

Corresponding author

Correspondence to Angelo Antonini.

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The authors confirm that the ethics board clearance was not required for this work. Written consent was obtained where needed. We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

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The authors declare no competing interests.

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Carrer, T., Bonato, G., Sandre, M. et al. Rapidly progressive multiple system atrophy in a patient carrying LRRK2 G2019S mutation. Neurol Sci 45, 309–313 (2024). https://doi.org/10.1007/s10072-023-07056-5

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  • DOI: https://doi.org/10.1007/s10072-023-07056-5

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