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

• Main Authors: Tomokazu Kimizu, Shinobu Ida, Kentaro Okamoto, Hiroyuki Awano, Emma Tabe Eko Niba, Yogik Onky Silvana Wijaya, Shin Okazaki, Hideki Shimomura, Tomoko Lee, Koji Tominaga, Shin Nabatame, Toshio Saito, Takashi Hamazaki, Norio Sakai, Kayoko Saito, Haruo Shintaku, Kandai Nozu, Yasuhiro Takeshima, Kazumoto Iijima, Hisahide Nishio, Masakazu Shinohara
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: International Journal of Neonatal Screening
• Subjects: spinal muscular atrophy; <i>SMN1</i>; deletion; incidence; newborn screening
• Online Access: https://www.mdpi.com/2409-515X/7/3/45

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 (<i>SMN1</i>) deletion. We analyzed the distribution of clinical subtypes and ages at genetic testing in the <i>SMN1</i>-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.