SMA: diagnosis at birth can save lives but newborn screening is a right only in 11 Regions

Sitting with head control, crawling, walking: gestures discounted for all children but unthinkable, until a few years ago, for children with Spinal Muscular Atrophy (Sma), a rare genetic disease that progressively compromises the ability to walk and, in the most serious cases, to swallow and breathe. Once many children affected by more severe forms of SMA died in the first years of life. Today that’s no longer the case: they exist treatments which, if administered promptly, allow the little ones to have a life comparable to that of their peers. As in the case of gene therapywhich intervenes directly on the genetic defect with a single intravenous infusion and, from 2021And paid by the National Health Service for SMA type 1, the most severe form. Now, thanks toextension of the criteria Of refundability by Aifathe Italian Medicines Agency, is also available for children with SMA 2 who have a maximum weight of 13.5 kg and for those pre-symptomatic with three copies of the SMN2 gene.

Sma 1 and Sma 2: symptoms and consequences

Spinal muscular atrophy or SMA, from its English acronym Spinal muscular atrophyit’s still there main genetic cause of death in childhood in the world. This rare neuromuscular disease “attacks” motor neurons, i.e. the nerve cells in the spinal cord responsible for sending impulses from the central nervous system to the muscles. Here’s why it can compromising the acquisition of motor skills, swallowing and breathing. Patients do not produce a sufficient quantity of the SMN – Survival Motor Neuron protein, necessary for the survival of motor neurons, but may have a variable number of backup copies of a second gene, SMN2, therefore maintaining a functionality, albeit partial, of the SMN protein. From here the variability of the forms of SMA and also of the symptoms.
It is estimated that in Italy it affects approximately one child for every 10 thousand newborns, so every year 40-50 children are born with SMA.

There more severe and more frequent form (60% of cases) is the Type 1 SMA. The debut of symptoms happens within the first six months of life: the little ones have a serious delay in the acquisition of motor stages, they do not have the ability to control their head or maintain a sitting position. The disease also compromises the acquisition of swallowing and breathing skills. Without mechanical respiratory assistance, children with SMA 1 cannot survive beyond two years.

AND serious also there Type 2 SMA: children have a greater number of copies of the SMN2 gene, so the onset of the disease occurs a little later, between 6 and 18 months, with less severe symptoms compared to type 1 SMA: children can sit but cannot walk independently in most cases. Life expectancy for those with SMA 2 it is extremely variable: with appropriate treatment, especially for respiratory failure, the majority of patients survive beyond adult life, even if they do not achieve independent walking. Over 30 percent of patients with SMA 2, however, die by the age of 25.

Ddiagnosis possible in the first days of life

More early he comes administered gene therapy (and also the other treatments available for SMA), a lot the more effective the resultsas the director of the NeMo pediatric clinical center of the Gemelli IRCSS university hospital in Rome, Marika Pane, associate professor of child neuropsychiatry at the Catholic University, explains: «According to the clinical studies available, the children who receive the therapy before symptoms appear they are able to accomplish the same stages of motor development of their peers.” This is why it is important timely diagnosis, possible thanks to neonatal screening for SMA performed in the first hours of life. If the test is positive, the newborns are taken care of by the SMA Reference Centers. To date, however, this opportunity Not And offered to all children who are born in Italy, despite the fact that the relevant legislation was changed in 2019, which extended neonatal screening to other rare genetic diseases. Nevertheless, Diagnosis at birth can make the difference between life and death.

Screening active in 11 Regions

Waiting for Decree updating the list of pathologies which at national level give the right to newborn screening, different regions have decided, with their own measures, to include the SMA (and other congenital diseases) in regional screening programs or to start pilot projects. According to a survey by OMaR-Osservatorio Malattie Rare, updated to January 2024, there are There are 11 regions in which neonatal screening for SMA is active.

Right of every newborn

“There are unacceptable inequalities between children – comments Anita Pallara, president of the association Sma families –. If you are born in a region where the test is carried out, you have the right to timely diagnosis and treatment; otherwise, the risk of a delay in diagnosis can lead to even unfortunate outcomes. Newborn screening must be a right of every newborn throughout Italy – reinforces Pallara –. When we were received at the Ministry of Health, they told us that the ministerial decree updating the list of pathologies to be tested was about to be signed. Then, secondlywe were told that newborn screening it would have been offered to all children who are born in Italy with the entry into force in April (postponed to January 1, 2025, ed) of the new outpatient services guaranteed within the Leathe essential levels of assistance. In the third measure we were told that the Regions have received funds to carry out newborn screening for SMA, even if we don’t know it. We no longer understand what the truth is.”

At the end of March, the general director of health planning at the Ministry of Health, Americo Cicchetti, announced that «the postponement of the entry into force of the new tariffs does not entail any delay for the start of newborn screening for diseases such as SMA. The provision is in fact resource-free, meaning it does not provide for greater burdens for the State. The 2019 Budget Law increased the resources allocated to the Regions for newborn screening. Some Regions have started them some time ago, others have not, and it is important that they guarantee this service. The Ministry of Health is alongside patients and ready to support those Regions which have not yet started screening even though the financial coverage».
The fact remains that children’s lives affected by SMA cannot depend on tortuous procedures and bureaucratic delays.

Diseases on the waiting list

Based on Law n.167/2016 every child born in Italy has right to extended newborn screening (Sne), mandatory and free, for over 40 hereditary metabolic diseases for which treatments are available, identified by a ministerial decree. In 2017 it Sne was inserted in the essential levels of assistance (Prime Ministerial Decree of 12 January 2017 updating the Leas, art. 38, paragraph 2), i.e. the benefits and services that must be guaranteed to every citizen throughout the national territory.
There Budget Law 2019 (art.1 paragraph 544) has extended neonatal screening to genetic neuromuscular diseases, severe congenital immunodeficiencies and lysosomal storage diseases and has established the “at least biennial” update of the “list of pathologies to be searched for through neonatal screening, in relation to evolution over time of scientific evidence in the diagnostic-therapeutic field for hereditary genetic diseases”.
The ENS Working Group, established in 2020 at the Ministry of Health, gave a positive opinion on the inclusion of SMA (and other diseases) in the list of pathologies to be tested with the ENS.
Among the congenital diseases for which treatments are available, they are waiting to be included in the list of those to be tested with the ENS, in addition to Smasome lysosomal pathologies such as mucopolysaccharidosis type I, Fabry, Gaucher and Pompe diseases, severe combined immunodeficiencies (SCID), X-linked adrenoleukodystrophy, metachromatic leukodystrophy.