Alberta Spinal Muscular Atrophy Newborn Screening—Results from Year 1 Pilot Project

Abstract

Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by biallelic pathogenic/likely pathogenic variants of the survival motor neuron 1 (SMN1) gene. Early diagnosis via newborn screening (NBS) and pre-symptomatic treatment are essential to optimize health outcomes for affected individuals. We developed a multiplex quantitative polymerase chain reaction (qPCR) assay using dried blood spot (DBS) samples for the detection of homozygous absence of exon 7 of the SMN1 gene. Newborns who screened positive were seen urgently for clinical evaluation. Confirmatory testing by multiplex ligation-dependent probe amplification (MLPA) revealed SMN1 and SMN2 gene copy numbers. Six newborns had abnormal screen results among 47,005 newborns screened during the first year and five were subsequently confirmed to have SMA. Four of the infants received SMN1 gene replacement therapy under 30 days of age. One infant received an SMN2 splicing modulator due to high maternally transferred AAV9 neutralizing antibodies (NAb), followed by gene therapy at 3 months of age when the NAb returned negative in the infant. Early data show that all five infants made excellent developmental progress. Based on one year of data, the incidence of SMA in Alberta was estimated to be 1 per 9401 live births.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…NBS for SMA was begun on 28 February 2022 and included a qPCR screening assay to detect the absence of SMN1 exon 7, which was multiplexed with an already established SCID qPCR assay allowing for a smooth cost-effective implementation. The results of screening 47,005 newborns during the first year of the program (prevalence of 1:9401) were recently reported [ 369 ]. NBS for classical galactosemia (galactose transferase deficiency—GALT) has been ongoing since April 2019, using a two-tier screening approach, which secondarily identifies infants with glucose-6-phosphate dehydrogenase (G6PD) deficiency.…”

Systematic Review of Newborn Screening Programmes for Spinal Muscular Atrophy

“…The review identified 37 cohort studies of newborn screening for SMA [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. No RCTs of newborn screening were identified.…”

“…Cohort studies relating to newborn screening programmes for SMA were identified from the following 17 countries ( Table 1 ): the UK [ 9 ], Belgium [ 10 , 11 , 12 ], Germany [ 13 , 14 , 15 , 16 , 17 , 18 ], Italy [ 19 , 20 ], Latvia [ 21 ], Portugal [ 22 ], Poland [ 23 ], Ukraine [ 24 ], Norway [ 25 ], Australia [ 26 , 27 , 28 , 29 ], the USA, Canada [ 30 , 31 , 32 ], Brazil [ 45 ], Japan [ 46 , 47 , 48 , 49 , 50 ], Taiwan [ 51 , 52 ], China [ 53 , 54 , 55 ] and Russia [ 56 , 57 ]. The USA screening programmes were reported for several US states: California [ 33 ], Georgia [ 34 ], Kentucky [ 35 ], Massachusetts [ 36 , 37 ], New York [ 38 , 39 , 40 ], North Carolina [ 41 ], Wisconsin [ 42 ], Utah [ 43 ] and Ohio [ 44 ].…”

A Study on the Incidence and Prevalence of 5q Spinal Muscular Atrophy in Canada Using Multiple Data Sources

“…SMA newborn screening has recently been implemented in many provinces and territories across Canada, which will help to provide more accurate incidence estimates of SMA by geographic location. 21,25 One recent study by Kernohan and colleagues included data from the first year of SMA newborn screening in Ontario; 139,900 newborns were tested and five were confirmed with SMA, which represented a birth prevalence of 1 in 27,960 live births during 2020-2021. 26 This birth prevalence is in line with the combined rates from CPSP and CNDR observed in the current study of 1 in 25,951.…”