2024-05-12 05:31:16
For spinal muscular atrophy, the main genetic cause of death in childhood, there are therapies today which, if administered immediately, allow children to have a normal or almost normal life; however, it is necessary to access it before symptoms appear
Sitting while controlling your head, crawling, walking: gestures that are taken for granted 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 cases more serious, to swallow and breathe. Once upon a time, many children affected by the most severe forms of SMA died in their first years of life. Today this is no longer the case: there are treatments that, if administered promptly, allow children to have a life comparable to that of their peers. As in the case of gene therapy, which intervenes directly on the genetic defect with a single intravenous infusion and, from 2021, is paid for by the National Health Service for type 1 SMA, the most serious form. Now, thanks to the extension of the reimbursement criteria by Aifa, the Italian Medicines Agency, it is also available for children with SMA 2 who have a maximum weight of 13.5 kg and for pre-symptomatic ones with three copies of the SMN2 gene.
Sma 1 and Sma 2: symptoms and consequences
Spinal muscular atrophy or SMA, from the English acronym Spinal muscular atrophy, is still the 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. This is why it can compromise 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 they may have a variable number of backup copies of a second gene, SMN2, therefore maintaining a functionality, albeit partial, of the SMN protein. Hence 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.
The most severe and most frequent form (60% of cases) is type 1 SMA. The onset of symptoms occurs within the first six months of life: children have a serious delay in the acquisition of motor stages, they do not have the ability to control the 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.
Type 2 SMA is also serious: 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 than type 2 SMA. type 1: the little ones can sit but cannot walk independently in most cases. Life expectancy for those with SMA 2 is extremely variable: with appropriate treatment, especially for respiratory failure, the majority of patients survive beyond adulthood, even if they do not achieve independent walking. Over 30 percent of patients with SMA 2, however, die by the age of 25.
Diagnosis possible in the first days of life
The earlier gene therapy is administered (and also the other treatments available for SMA), the more effective the results are, as explained by the director of the NeMo pediatric clinical center of the Gemelli IRCSS university hospital in Rome, Marika Pane, associate professor of Neuropsychiatry at the Catholic University: «According to the available clinical studies, children who receive therapy before the symptoms appear are able to complete the same stages of motor development as their peers». This is why timely diagnosis is important, which is 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 is not offered to all children born in Italy, despite the relevant legislation being amended in 2019, which extended neonatal screening to other rare genetic diseases. Yet, diagnosis at birth can make the difference between life and death.
Screening active in 11 Regions
While waiting for the Decree to update the list of pathologies that give the right to newborn screening at a national level, several Regions have decided, with their own provisions, to include SMA (and other congenital diseases) in regional screening programs or to launch pilot projects. According to a survey by OMaR-Osservatorio Malattie Rare, updated in January 2024, 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 unfortunate outcomes. Newborn screening must be the 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, secondly, we were told that newborn screening would be offered to all children born in Italy with the entry into force in April (postponed to January 1, 2025, ed.) of the new outpatient services guaranteed under of the LEAs, the essential levels of assistance. Thirdly, we were told that the Regions have received the funds to carry out neonatal screening for SMA, even if we are not aware of 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 in the start of neonatal screening for diseases such as SMA. The measure 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 that have not yet started screening even though financial coverage exists.”
The fact remains that the lives of children affected by SMA cannot depend on tortuous procedures and bureaucratic delays.
Diseases on the waiting list
Based on Add n.167/2016 every child born in Italy has the right to extended newborn screening (ENS), mandatory and free, for over 40 hereditary metabolic pathologies for which treatments are available, identified by a ministerial decree. In 2017 the ENS was included 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.
The 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, in addition to SMA, some lysosomal pathologies such as type I mucopolysaccharidosis, Fabry, Gaucher and Pompe diseases, combined immunodeficiencies are waiting to be included in the list of those to be tested with the ENS. severe (SCID), X-linked adrenoleukodystrophy, metachromatic leukodystrophy.
11 maggio 2024
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