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. 2021 Jul 20;7(3):45.
doi: 10.3390/ijns7030045.

Spinal Muscular Atrophy: Diagnosis, Incidence, and Newborn Screening in Japan

Tomokazu Kimizu  1 , Shinobu Ida  2 , Kentaro Okamoto  3 , Hiroyuki Awano  4 , Emma Tabe Eko Niba  5 , Yogik Onky Silvana Wijaya  5 , Shin Okazaki  6 , Hideki Shimomura  7 , Tomoko Lee  7 , Koji Tominaga  8 , Shin Nabatame  8 , Toshio Saito  9 , Takashi Hamazaki  10 , Norio Sakai  11 , Kayoko Saito  12 , Haruo Shintaku  10 , Kandai Nozu  4 , Yasuhiro Takeshima  7 , Kazumoto Iijima  4   13 , Hisahide Nishio  5   14 , Masakazu Shinohara  5
Affiliations

Spinal Muscular Atrophy: Diagnosis, Incidence, and Newborn Screening in Japan

Tomokazu Kimizu et al. Int J Neonatal Screen. .

Abstract

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder that causes degeneration of anterior horn cells in the human spinal cord and subsequent loss of motor neurons. The severe form of SMA is among the genetic diseases with the highest infant mortality. Although SMA has been considered incurable, newly developed drugs-nusinersen and onasemnogene abeparvovec-improve the life prognoses and motor functions of affected infants. To maximize the efficacy of these drugs, treatments should be started at the pre-symptomatic stage of SMA. Thus, newborn screening for SMA is now strongly recommended. Herein, we provide some data based on our experience of SMA diagnosis by genetic testing in Japan. A total of 515 patients suspected of having SMA or another lower motor neuron disease were tested. Among these patients, 228 were diagnosed as having SMA with survival motor neuron 1 (SMN1) deletion. We analyzed the distribution of clinical subtypes and ages at genetic testing in the SMN1-deleted patients, and estimated the SMA incidence based on data from Osaka and Hyogo prefectures, Japan. Our data showed that confirmed diagnosis by genetic testing was notably delayed, and the estimated incidence was 1 in 30,000-40,000 live births, which seemed notably lower than in other countries. These findings suggest that many diagnosis-delayed or undiagnosed cases may be present in Japan. To prevent this, newborn screening programs for SMA (SMA-NBS) need to be implemented in all Japanese prefectures. In this article, we also introduce our pilot study for SMA-NBS in Osaka Prefecture.

Keywords: SMN1; deletion; incidence; newborn screening; spinal muscular atrophy.

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Conflict of interest statement

T.K. reports personal compensation from Biogen Japan and Novartis Japan, and grant support from Novartis Japan. S.I. reports grant support from Novartis Japan. H.A. reports personal compensation from Biogen Japan and Novartis Japan, and grant support from Novartis Japan. H.S. (Hideki Shimomura) reports personal compensation from Biogen Japan. T.S. reports personal compensation from Biogen Japan. T.H. reports personal compensation from Biogen Japan and Novartis Japan. K.S. reports personal compensation from Biogen Japan, Novartis Japan and Chugai Pharmaceutical Co. and grant support from Biogen Japan and Novartis Japan. H.S. (Haruo Shintaku) reports personal compensation from Biogen Japan. K.N. reports grant support from Novartis Japan. Y.T. reports personal compensation from Biogen Japan and Novartis Japan, and grant support from Novartis Japan, and consulting fee from Chugai Pharmaceutical Co. K.I. reports grant support from Novartis Japan. H.N. reports personal compensation from Biogen Japan, Novartis Japan, and Chugai Pharmaceutical Co., and a consulting fee from Sekisui Medical Co. M.S. reports personal compensation and grant support from Biogen Japan. The companies had no role in the design, execution, interpretation, or writing of the study. The other co-authors declare no competing interests.

References

    1. Nurputra D.K., Lai P.S., Harahap N.I.F., Morikawa S., Yamamoto T., Nishimura N., Kubo Y., Takeuchi A., Saito T., Takeshima Y., et al. Spinal Muscular Atrophy: From Gene Discovery to Clinical Trials. Ann. Hum. Genet. 2013;77:435–463. doi: 10.1111/ahg.12031. - DOI - PubMed
    1. Verhaart I.E.C., Robertson A., Wilson I.J., Aartsma-Rus A., Cameron S., Jones C.C., Cook S.F., Lochmüller H. Prevalence, Incidence and Carrier Frequency of 5q-Linked Spinal Muscular Atrophy—A Literature Review. Orphanet J. Rare Dis. 2017;12:124. doi: 10.1186/s13023-017-0671-8. - DOI - PMC - PubMed
    1. Lefebvre S., Bürglen L., Reboullet S., Clermont O., Burlet P., Viollet L., Benichou B., Cruaud C., Millasseau P., Zeviani M., et al. Identification and Characterization of a Spinal Muscular Atrophy-Determining Gene. Cell. 1995;80:155–165. doi: 10.1016/0092-8674(95)90460-3. - DOI - PubMed
    1. Calucho M., Bernal S., Alías L., March F., Venceslá A., Rodríguez-Álvarez F.J., Aller E., Fernández R.M., Borrego S., Millán J.M., et al. Correlation between SMA Type and SMN2 Copy Number Revisited: An Analysis of 625 Unrelated Spanish Patients and a Compilation of 2834 Reported Cases. Neuromuscul. Disord. 2018;28:208–215. doi: 10.1016/j.nmd.2018.01.003. - DOI - PubMed
    1. Arnold W.D., Kassar D., Kissel J.T. Spinal Muscular Atrophy: Diagnosis and Management in a New Therapeutic Era. Muscle Nerve. 2015;51:157–167. doi: 10.1002/mus.24497. - DOI - PMC - PubMed