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

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.

The importance of SMA screening tests in newborns – review

“…According to the study, only 20.9% of patients with SMA type II were diagnosed in the proper time (according to scientists "proper" time for SMA type II is earlier than 18 months), while the rate for patients with SMA type I was 65.5% (the proper time, according to scientists, is up to 6 months after birth for SMA type I). For these reasons, scientists call for the implementation of screening for SMA, which will enable early treatment and maximum therapeutic benefit [21].…”

Stability and Oligomerization of Mutated SMN Protein Determine Clinical Severity of Spinal Muscular Atrophy

“…Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by defects of lower motor neurons in the spinal cord, resulting in weakness and wasting of voluntary muscles [ 1 ]. SMA is arguably the most common genetic disorder, with an incidence of approximately 1 in 6000 to 20,000 live births and a carrier frequency of 1/40–1/70 in the general population [ 2 , 3 , 4 , 5 ].…”

Changes in the Incidence of Infantile Spinal Muscular Atrophy in Shikoku, Japan between 2011 and 2020

“…In general, nearly all patients with SMA type 1 have one or two copies of SMN2 . Most patients with SMA type 2 have three copies of SMN2 , and most with SMA type 3 have three or four copies of SMN2 [ 2 , 5 , 6 ]. Patients with SMA type 4 usually have four copies or more [ 2 ].…”

“…SMA is a rare disease, and the incidence of SMA varies among countries [ 7 ]. Reports of SMA incidence before 1995 were based on clinical symptoms; however, after 1995, reports of SMA incidence were mainly based on genetic testing [ 6 ]. Currently, the number of SMA incidence research reports based on newborn screening (NBS) is increasing [ 8 ].…”