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. 2024 Apr;11(4):938-945.
doi: 10.1002/acn3.52011. Epub 2024 Jan 29.

Nationwide survey of patients with multisystem proteinopathy in Japan

Satoshi Yamashita  1   2 , Yuji Takahashi  3 , Jun Hashimoto  4 , Ayuka Murakami  5 , Ryoichi Nakamura  5   6 , Masahisa Katsuno  5   7 , Rumiko Izumi  8 , Naoki Suzuki  8 , Hitoshi Warita  8 , Masashi Aoki  8 ; Japan MSP Study Group
Collaborators, Affiliations

Nationwide survey of patients with multisystem proteinopathy in Japan

Satoshi Yamashita et al. Ann Clin Transl Neurol. 2024 Apr.

Abstract

Objective: Multisystem proteinopathy (MSP) is an inherited disorder in which protein aggregates with TAR DNA-binding protein of 43 kDa form in multiple organs. Mutations in VCP, HNRNPA2B1, HNRNPA1, SQSTM1, MATR3, and ANXA11 are causative for MSP. This study aimed to conduct a nationwide epidemiological survey based on the diagnostic criteria established by the Japan MSP study group.

Methods: We conducted a nationwide epidemiological survey by administering primary and secondary questionnaires among 6235 specialists of the Japanese Society of Neurology.

Results: In the primary survey, 47 patients with MSP were identified. In the secondary survey of 27 patients, inclusion body myopathy was the most common initial symptom (74.1%), followed by motor neuron disease (11.1%), frontotemporal dementia (FTD, 7.4%), and Paget's disease of bone (PDB, 7.4%), with no cases of parkinsonism. Inclusion body myopathy occurred most frequently during the entire course of the disease (81.5%), followed by motor neuron disease (25.9%), PDB (18.5%), FTD (14.8%), and parkinsonism (3.7%). Laboratory findings showed a high frequency of elevated serum creatine kinase levels and abnormalities on needle electromyography, muscle histology, brain magnetic resonance imaging, and perfusion single-photon emission computed tomography.

Interpretation: The low frequency of FTD and PDB may suggest that FTD and PDB may be widely underdiagnosed and undertreated in clinical practice.

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Conflict of interest statement

All the authors have stated explicitly that there are no conflicts of interest in connection with this article.

Figures

Figure 1
Figure 1
(A) Histogram of age at onset of secondary survey participants. (B) Histogram of age at diagnosis of secondary survey participants. (C) Histogram of age at last follow‐up of secondary survey participants. (D) MSP categories of secondary survey participants. (E) Familial history of secondary survey participants. (F) Genetic testing of secondary survey participants. (G) Initial symptoms of secondary survey participants. (H) Clinical symptoms of the entire course of the disease in secondary survey participants. (I) Severity classification assessed at diagnosis and last follow‐up. (J) Laboratory findings in secondary survey participants. (K) Muscle biopsy findings in secondary survey participants.
Figure 2
Figure 2
Combination of clinical manifestations of the entire course of the disease in MSP subtypes. Numbers indicate number of patients.
See this image and copyright information in PMC

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