From December 2021 to April 2024, over 65 thousand newborns from Puglia underwent neonatal screening for SMA, with 8 presymptomatic positive diagnoses and none in the symptomatic phase
The Puglia has appeared, since the approval of Regional Law no. 4 of 19 April 2021, as the Italian region pioneers in introducing mandatory screening at birthspinal muscular atrophy (SMA)starting from December 6, 2021. A study, published in Annals of Clinical and Translational Neurologyit was proposed to evaluate the impact of NBS implementation in Italy on accessibility to care and patient outcomesusing the example of Puglia.
Pioneering pilot studies promoted the implementation of NBS for SMA in different countries of the world and, combined with the opportunity to treat newborns in the presymptomatic phase, provided the first concrete evidence of the effectiveness of early treatment in SMA, prompting these initiatives to spread worldwide. A recent Italian pilot study on a 2-year experience demonstrated that neonatal screening led to the identification of 15 newborns with a molecular diagnosis of SMAhighlighting the importance of standardizing current molecular diagnostic techniques.
THE PUGLIESE CASE STUDY
From December 6, 2021, children born in any of the 26 birth centers in Puglia were screened for SMA within the regional NBS initiative. The samples were sent to the reference Medical Genetics Unit (Venus Hospital in Bari) and a real-time PCR-based test specific for the qualitative detection of the SMN1 gene of exon 7.
For newborns presumed positive to the screening, tests were performed two molecular diagnostic confirmation tests on fresh blood samples only after obtaining parental consent, both used to confirm the homozygous deletion of SMN1 exon 7 and to determine the number of copies of SMN2.
All positive subjects received one of the two therapies approved for presymptomatic SMA in ItalyPatients underwent a pretreatment motor nerve conduction study (NCS) to record baseline compound muscle action potential (CMAP) from pulse stimulation and were followed prospectively with blood samples and neurological examinations.
The study was written by pediatric neurologists, biologists, and geneticists from the Dino Ferrari Center of the University of Milan, the Giovanni XXIII Pediatric Hospital in Bari, and the Di Venere Hospital in Bari.
THE RESULTS
In the first 20 months following the introduction of regional neonatal screening initiatives for SMA, the examination of 42,492 children screened highlighted a positive result in four newborns (0.009% of the total), confirmed in all cases. This event resulted in a annual incidence rate of 1 in 10,623 births. Communication of the diagnosis and information about treatment options were guided by a team consisting of a pediatric neurologist, a geneticist, and a genetic counselor. Parents of all four children consented to confirmatory genetic testing and participation in the study.
Analyzing the complete case study – collected by Fabiano Amati, Regional Councilor of Puglia, President of the Regional Budget and Programming Commission – since the start of the pilot project (December 2021) to the last diagnosed case (April 2024), the data collected are the following:
- Case 1 – SMA 1. Date of birth April 4, 2022; date of diagnosis April 11, 2022 (after 7 days from birth); date of gene therapy administration April 27, 2022 (after 23 days from birth and 16 days from diagnosis). To date (April 2024) no signs of disease and walking.
- Case 2 – SMA 2 or 3. Date of birth June 10, 2022; date of diagnosis June 17, 2022; date of start of non-gene therapy July 1, 2022. To date (April 2024) no signs of disease and walking.
- Case 3 – SMA 1. Date of birth October 29, 2022; date of diagnosis November 7, 2022 (after 9 days from birth); date of gene therapy administration November 18, 2022 (after 20 days from birth and 11 days from diagnosis). To date (April 2024) no signs of disease and first steps;
- Case 4 – SMA 1. Date of birth May 31, 2023; date of diagnosis June 7, 2023 (after 7 days from birth); date of gene therapy administration June 16, 2023 (after 16 days from birth and 9 days from diagnosis). To date (April 2024) some slight signs of disease, but recovering.
- Case 5 – SMA 1. Date of birth October 6, 2023; date of diagnosis October 12, 2023 (after 6 days from birth); date of gene therapy administration October 19, 2023 (after 13 days from birth and 7 days from diagnosis). To date (April 2024) no signs of disease and growth process consistent with age.
- Case 6 – SMA 4. Date of birth October 17, 2023; date of diagnosis October 24, 2023; date of start of non-gene therapy November 6, 2023. To date (April 2024) no signs of disease and growth process consistent with age.
- Case 7 – SMA 2 or 3. Date of birth November 28, 2023; date of diagnosis December 6, 2023; date of start of non-gene therapy November 13, 2023. To date (April 2024) no signs of disease and growth process consistent with age.
- Case 8 – SMA 1. Date of birth March 30, 2024; date of diagnosis April 4, 2024 (after 5 days from birth); date of gene therapy April 12, 2024 (after 13 days from birth and 8 days from diagnosis).
To these – he says Anita Pallara, President of the SMA Families Association – add the story of the 9-month-old Palestinian baby that Puglia welcomed a few months ago. The little boy, suffering from SMA 1 and coming from Ramallah, had no possibility of being treated in his country due to the reduction in the supply of medicines caused by the ongoing war between Israel and Hamas. Once he arrived in Bari, he was administered gene therapy and is now being monitored by Italian clinicians.
We remind you that in Italy there is still no national legislation that guarantees screening for SMA but each territory manages itself autonomously. In fact, they are 12 regions where screening is activeincluding Puglia, and four of which appear to be ready to leave soon.
In conclusion, – write the authors of the study – The successful start of the SMA-NBS study in Puglia has illuminated the path towards early diagnosis and treatment throughout the country. While acknowledging the benefits, the study emphasizes the need for equity in newborn screening programs, with the goal of mandating SMA screening across Italy. The path ahead includes refining workflows, enhancing medical education, and promoting greater awareness to ensure rapid and equitable implementation of SMA-NBS across the nation.
