P.072 Alberta Spinal Muscular Atrophy Newborn Screening (SMA-NBS) – 2022 results

Abstract

Background: Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by biallelic mutations of the survival motor neuron 1 (SMN1) gene. Early diagnosis via newborn screening and presymptomatic treatment are essential to optimize health outcomes for affected individuals. Methods: We developed a multiplex real-time polymerase chain reaction assay using dried blood spot samples for the detection of homozygous deletion of exon 7 of the SMN1 gene. Newborns who were screened positive were seen urgently for clinical evaluations. Copy numbers of SMN1 and SMN2 genes were determined by multiplex ligation-dependent probe amplication for confirmatory testing. Results: From February 28, 2022 to December 31, 2022, 42,450 newborns were screened in Alberta. Four infants had abnormal screen results and were subsequently confirmed to have SMA. No false positive newborns were detected. Three infants received adeno-associated virus serotype 9 (AAV9)-mediated SMN1 gene replacement therapy <31 days of age. One infant received SMN2-splicing modulator treatment due to maternally-transferred AAV9 neutralizing antibodies prior to gene therapy at 3 months of age. Conclusions: The estimated incidence of SMA in Alberta is 9.4 (95% CI: 2.5 – 24.1) per 100,000 live-births. During the first year of the SMA-NBS program, 4 asymptomatic infants received treatment and demonstrated excellent developmental progress to date.