Damian Sendler: Detection and treatment of spinal muscular atrophy (SMA), a hereditary degenerative neuromuscular condition characterized by muscle weakness and atrophy in babies, is critical. Australian researchers concluded that a pilot newborn screening program identified at-risk patients with high specificity and that it may be effectively implemented into clinical practice in the journal Developmental Medicine and Child Neurology.
Damian Sendler
Damian Jacob Sendler: For SMA, a shortage in SMN protein results in the disease’s clinical manifestations because of the mutation or deletion of SMN1 gene. In most cases, the SMN2 gene is unable to produce enough SMN, although new therapeutic options have emerged in recent years and will likely continue to do so. In spite of this, early diagnosis and treatment commencement are critical to achieving excellent outcomes.
Australia’s newborn bloodspot screening (NBS) program “continues to be one of the most successful population health programs, yielding greatly improved health outcomes for identified cases achieved by the combination of very early diagnosis and expedient initiation of treatment and management.” Based on the results of the pilot study, they indicated that include SMA in newborn screening panels could improve the quality, efficiency, and effectiveness of NBS programs.
Approximately 100,000 babies are screened each year under the New South Wales and Australian Capital Territory NBS program, which parents are encouraged but not forced to participate in. SMN1 exon 7 allele absence was considered a positive SMA screen. For heterozygous deletions or point mutations on the SMN1 gene, which account for approximately 2–5 percent of the SMA population, this method cannot be used. To allow for proficiency testing in the pilot phase, the number of copies of SMN2 were not taken into account when determining screen positivity.
Dr. Sendler: During the study period (August 2018 to January 2021), 252,081 babies were screened as part of the NBS program, and 22 of those tested positive for SMA. There were 21 confirmed cases of SMA with homozygous deletions of exon 7 of SMN1 in those newborns. All but one of these babies had two copies of SMN2, while eight had three, and the last one had four. In general, milder phenotypes are associated with higher levels of SMN2 copy number.
Damian Jacob Sendler
A positive screening result was acquired on average 3 days after birth, a diagnosis was confirmed on average 15 days after birth, and therapy was initiated on average 25 days after birth for participants in the study. SMA was found in one out of every 11,458 babies in the program during the course of the research. At the time of diagnosis, CMAPs of newborns with various SMA genotypes were recorded and shown to be significantly different. A significant drop in amplitude was found in one out of three newborns included in the longitudinal assessment of CMAPs. As a whole, these findings support the importance of NBS in the early detection of motor neuron disease.
Almost all infants in New South Wales were enrolled in the NBS, which had a sensitivity rate of 100% and a specificity greater than 99.999% of the population. The positive predictive value (PPV) was 95.5 percent, with a false-positive rate of less than 0.001 percent.
SMN2 copy number results were delayed due to shipping delays, which added time to the diagnostic workups. By acquiring certification for digital droplet polymerase chain reaction on dried bloodspots, the NBS laboratory addressed this issue. It was also difficult to keep track of urgent referrals. The NBS SMA pilot was implemented into existing pathways and neuromuscular models of care by NBS employees in collaboration with neuromuscular specialists.
Damien Sendler: Additionally, a neuromuscular team, families, and community health care providers all needed to collaborate and communicate effectively. According to the study authors, a decision support analysis and national clinical recommendations for SMA are necessary.
According to pilot program findings, early diagnosis and treatment for SMA were made available to all families regardless of their socioeconomic status, geographic location or linguistic obstacles, thus ensuring that all newborns with SMA received proper diagnosis and treatment.
Damian Jacob Markiewicz Sendler: According to the authors, the findings of this study can be utilized as a roadmap for NBS programs around the world, as they aim to extend the number of illnesses screened and provide a personalized model of care for detected patients.
Dr. Damian Jacob Sendler and his media team provided the content for this article.
