[LS9] Luncheon Seminar 9: SMA: Diagnosis of Spinal Muscular Atrophy as Genetic Disease

[LS9-3A-1] Genetic Diagnosis of Spinal Muscular Atrophy and Newborn Mass Screening in Taiwan

^○Yin-Hsiu CHIEN^{1, 2} (1.Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan, 2.Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan)

The first therapy for spinal muscular atrophy (SMA) has been approved in the United Sates in Dec. 2016. Due to the rapid and profound loss of motor neurons in patients especially in type I SMA, presymptomatic diagnosis expects to help patients achieve the best therapeutic effects. Therefore we initiated a pilot SMA newborn screening (NBS) program in 2014 to demonstrate the feasibility of a presymptomatic SMA diagnosis through NBS. A real-time PCR (RT-PCR) genotyping assay for homozygous SMN1 deletion using dried blood spot (DBS) samples was incorporated into the routine newborn metabolic screening at the National Taiwan University Hospital newborn screening center. If the first screen showed SMN1 homozygous deletion, a second-tier test for SMN1 status and SMN2 copy number were determined by droplet digital PCR (ddPCR) using the original screening DBS. Another whole blood sample for multiplex ligation-dependent probe amplification (MLPA) was requested to confirm the screening result. Of the 144,509 newborns screened, 18 tested positive according to the RT-PCR assay. The DBS ddPCR assay excluded ten false-positives, and the other eight patients were confirmed by the MLPA assay. The SMA incidence was 1 in 18,000. Two of the three patients with 2 copies of SMN2 and all five patients with 3 or 4 copies of SMN2 were asymptomatic at the time of diagnosis. Newborn screening detects patients affected by SMA before symptom onset and enables early therapeutic intervention. The inclusion of a second-tier DBS ddPCR screening assay resulted in a positive prediction rate of 100%.