Aftermath of the pilot project on neonatal screening for spinal muscular atrophy in the City of Saint Petersburg, Russia. Organizational, diagnostic and clinical aspects

Spinal muscular atrophy (SMA) is one of the most frequent and severe hereditary diseases that leads to the destruction of motor neurons in the spinal cord and muscle weakness and is resulted from mutations in the SMN1 gene. The purpose of this research was to identify homo- and heterozygous mutations in the SMN1 gene in newborns. Materials and methods used: a multicenter prospective open continuous screening study of newborns at the age of 4 DoL (for full-term)/7 DoL (for preterm). The screening was carried out in Dec. 30, 2021-Nov. 17, 2022 on the basis of 21 obstetrics facilities located within the City of Saint Petersburg (Russia). Results: 36,140 participants (17,687 (49%) boys/18,453 (51%) girls) of the neonatal screening; 77 (0.21%) parents/caretakers have refused to participate. A technique for detecting homo- and heterozygous deletions in the SMN1 gene was developed based on rapid DNA extraction from dried blood spots followed by the real-time PCR. The project had identified 4 patients with SMA, two of whom had two and the other two had three copies of the SMN2 gene. The period of time needed to set the diagnosis ranged from 7th to 14th DoL. All of these patients have received the gene replacement therapy for a period of 3 to 5 months. There was a positive trend as a result of the therapy in all of the cases. 772 SMA carriers were also identified during the screening. 51% of their parents/caretakers have been followingly consulted on the possible risks of the disease. The frequency of SMA in the City of Saint Petersburg was 1 in 9035 newborns with a carrier frequency of 1 in 47. The sensitivity and specificity of the test were determined, which were 99.74% and 100%, respectively. Conclusion: SMA screening has been tested and put into practice. The conducted project of neonatal screening for SMA in the City of Saint Petersburg has demonstrated the readiness of its residents and the municipal healthcare system, the practitioners and organizers to this type of medical solution. The described developed methodology has demonstrated its effectiveness in terms of early detection of patients and carriers of this disease.