Neonatal screening: at least 7 other diseases are to be added to the national list

Source: Shutterstock

Expand newborn screening also to SMA, Fabry, Gaucher, Pompe, MPS I, ADA Scid and Adrenoleukodystrophy in order to be able to intervene promptly, avoiding disability and early death. This is the appeal. "Today Europe looks to the country as a leader in newborn screening. With Law 167/2022 we were the first country, and currently the only one, to ensure that over 40 rare metabolic diseases are searched for on all newborns. which, if not taken in time, can lead to disability or premature death. This has helped to increase the attention of all of Europe on this issue and our example could also be a driving force for greater uniformity between the policies of the different countries members ". With these words the Prof. Maurizio Scarpa, Coordinator of the European MetabErn Network and Director of the Regional Reference Center for Rare Diseases of the Integrated University Health Authority of Udine opened the presentation event of the Book "SNE, prospects for extension of the panel", realized from the Rare Diseases Observatory (OMaR) with the sponsored by the Telethon Foundation and UNIAMO FIMR Onlus.   

The list to be updated with technical and medical progress

Our law also requires this list (so-called "panel") to be updated in line with technical and medical progress. To date at least 7 pathologies have the requisites for immediate inclusion in the panel.

They would be:

  1. spinal muscular atrophy (SMA),
  2. Gaucher's disease,
  3. Fabry's disease,
  4. Pompe disease,
  5. Mucopolysaccharidosis type I (MPS I),
  6. the ADA-Scid immunodeficiency
  7.  Brain Adrenoleukodystrophy (X-CALD)

This is what results, in summary, from the opinions expressed by a group of over 40 experts - selected from clinicians, representatives of scientific societies, laboratory staff and patient associations - who for 6 months worked on the creation of the OMaR Notebook dedicated to theme.        

"Screening is not only a great opportunity for early diagnosis and treatment, but it is also a very useful tool to give us more knowledge on the natural history of these diseases and to promote the development of therapies, and it will be very useful to clarify the numbers through registers, "he then added Prof. Scarpa, which also asks that "the theme be included in an organic way in the new National Plan for Rare Diseases".

"We hope that this work can serve to speed up the work of the commission - he explained Ilaria Ciancaleoni Bartoli, Director of OMaR - The deadline for the update is May 31: we hope it doesn't take even one more day, on the contrary, we hope it can take a little less. "The working groups have taken into consideration over 20 different pathologies analyzing the compliance with internationally recognized scientific criteria and also taking into account the existence of screening experiences, in the country or in the rest of the world, of the results obtained or of the critical issues that emerged. At the end of this analysis only 7 serious rare diseases to date, they have shown that they meet all the requisites required to enter screening, which does not mean that over the years the list may expand further when other therapies arrive or other tests are validated.

Rare diseases remained (for now) excluded

La PNP-Scid, a rare form of immunodeficiency, it could in fact be inserted as soon as the relative test receives the CE mark, while a further group of immunodeficienze could have the same consideration, but since they are detectable with TREC / KREC test, which not all laboratories are able to do, it would be necessary to provide an adequate time before the entry into force. "The initial idea of ​​this work was that of a 'one-off' notebook - he concluded Ciancaleoni Bartoli - but during the meetings we decided to make it an 'open notebook': we will therefore continue with periodic meetings up to, ideally, also involving the Regions, which play an important role in the screening implementation process ".      

Read also: Newborn, the first checks at birth

The screening paths

In the document Book "SNE, prospects for extension of the panel", realized from the Rare Diseases Observatory, final considerations are also reported relating to aspects that mainly concern the organization of screening programs. 

The reflections concern different aspects:

  1. on the one hand the patient's path, which must be well established even for late onset cases,
  2. on the other hand for the path of funding, which flow into an indistinct fund of the LEA but which must be effectively allocated by the relevant Regions to laboratories and take-over centers, as well as the optimization of the number of laboratories, which would also become an efficiency in spending.       

Taking charge of children and families

This morning the table involving the associations was dedicated to the first theme, that of taking care of children - and their families - who are diagnosed with a disease that could have an onset later in the years, and in a variable form, this morning was dedicated to the table that involved the associations. dealing with lysosomal diseases, those in which these cases are more frequent. In fact, all associations support the need to include Pompe, Gaucher, Fabry and MPS I diseases in screening since they believe that the long-term benefit, both for children and families, far outweighs the initial trauma of diagnosis and uncertainty about the timing of the onset of symptoms and therefore of the initiation of therapies. A judgment shared also by clinicians who underline the importance of establishing univocal paths, also through scientific consensus for these specific cases and the importance of always predicting the path psychological support for families.  

The organization of the system

As regards the organization of the system, on the other hand, there are two aspects that emerged strongly, the first concerns the organization of the laboratories: "In order to minimize the need for additional funds necessary for technical and personnel adaptation - said the Prof. Giancarlo La Marca, Director of the Enlarged Neonatal Screening Laboratory of the Meyer University Hospital of the city and President of SIMMESN - it would be useful to implement the process of reducing the number of screening laboratories going towards the respect of the optimal catchment area of ​​at least 60.000 newborns". A second point, also connected to this, concerns the financing of the screening process, from testing to taking charge. "Most regions have not yet adopted clear procedures with which to allocate and link national funds to the screening process and subsequent patient care - he continued The Brand - For this reason it would be advisable, for the future, to identify a mechanism that guarantees the specific destination of funds for the newborn screening process. This is an important and necessary prerequisite to guarantee a qualitatively satisfactory level of screening, with dedicated staff, and a uniform service throughout the territory, both for what is currently foreseen and for what will be following the expansion of the panel ".        

Neonatal screening: why insert the 7 new pathologies

  • Extremely effective therapies have arrived for the SMA and the test is already being done in Lazio and Tuscany.
  • For the diseases of Fabry, Gaucher, Pompe and MPS I, there have been therapies for years and in Del Paese there is a long experience in neonatal diagnosis
  • For the ADA Scid the test is simple, inexpensive, and there is even gene therapy available.
  • For adrenoleukodystrophy, the arrival of this option is a matter of weeks

Il Book "SNE, prospects for extension of the panel" edited by the Rare Diseases Observatory was drawn up taking into account the provisions of the Del Paesena legislation, which requires updating the list of "hereditary metabolic diseases, genetic neuromuscular diseases, lysosomal diseases and severe congenital immunodeficiencies "to be screened, analyzing them in the light of some established criteria. These are in particular the minimum requirements established by the WHO in 1995 - or Wilson and Jungner criteria - and the recommendations on newborn screening contained in the position paper prepared by Uniamo in 2022. Tables have been identified for each of these groups of diseases. of work composed of clinicians, biologists, researchers and patient associations with specific expertise and experience in the field who then discussed and verified the compliance of over 20 pathologies with the listed criteria and also evaluated the results of specific Del Paesene experiences also conducted through pilot projects and regional laws, as well as the latest news in the therapeutic field.                      

The working group that evaluated the neuromuscular diseases has taken three into consideration: 

  1. Spinal Muscular Atrophy (SMA),
  2. Duchenne muscular dystrophy
  3. and Congenital myotubular myopathy.

Of these only the first received a favorable opinion for inclusion in the Del Paeseno screening panel.


In fact, for this pathology today there are effective therapies that can be carried out a few weeks after birth and that the more they are done early, the more they change the history of the disease, the genetic test is already validated and a screening project involving Tuscany and Lazio, which started in September 2022, is already active in Del Paese, while similar projects should also be launched in Liguria and Piedmont soon: inclusion in the national panel would ensure that all newborns have the same opportunity, and in this specific case a diagnosis at birth can make the difference between life and death.           

"SMA is the condition that in recent years has given the best results from a therapeutic point of view: if in the past a child with the most severe form had little chance of survival beyond 2 years of age, today we can eliminate the word 'fatal "from the prognosis thanks to the new therapies. The results are very good already in babies who have manifested SMA. Even more exciting, it has been shown that by intervening quickly, within a few weeks of birth and before the signs of the condition manifest themselves, the children who would have been affected by the severe forms are no longer at risk of survival and moreover acquire the motor milestones at a similar age to unaffected children. Only a few years ago they would not even have acquired the sitting position. In the pilot project of newborn screening in Lazio and Tuscany, to date we have tested over 56.000 newborns and given, within 9 days of age, the diagnosis of SMA to 11 children, of which 8 are already being treated. The oldest is 8 months old and starts walking, "said the Prof. Francesco Danilo Tiziano of the Genomic Medicine Section of the Catholic University of the Sacred Heart.

Lysosomal diseases

The working group that evaluated the lysosomial diseases he had to face a longer job, since the diseases examined were 14, but of these only 4 received a favorable opinion on inclusion in the national panel: 

  1. Fabry disease,
  2. Gaucher disease,
  3. Pompe disease
  4. and Mucopolysaccharidosis type 1 (MPS I).

For these pathologies today there are effective therapies, both pharmacological and transplant, commercial tests available and validated and, moreover, there are regions that for years have already successfully carried out neonatal screening for these diseases. In Tuscany since 2022 the diseases of Fabry, Pompe and MPS I are searched for at birth, through the collection of drops of blood at 48-72 hours of age., while in 80% of Triveneto (all of Friuli, the province of Trento and the provinces of Padua, Venice, Treviso and Belluno) since 2022 in addition to these pathologies Gaucher disease is also being researched. Thanks to these projects, which have now been made stable thanks to the Regional Laws, 32 have emerged in Tuscany with Fabry and 11 with Pompe and in the Triveneto 18 children with Fabry disease have been identified, 8 with Gaucher, 26 with the Pompe and 2 with the MPS I.

"In the absence of newborn screening, the stories of our patients with Fabry disease are characterized by real diagnostic odyssey that last, in most cases, 13-25 years, with misdiagnoses and more specialists consulted. These patients live together for years. with severe pain in the hands and feet, cardiological and kidney problems up to insufficiency and dialysis, having or at risk of a juvenile stroke. Our screening experience has shown that following the diagnosis in a newborn infant, family members with affected and symptoms are often diagnosed. years in search of an answer. The therapies available are absolutely effective, but only if the diagnosis is early. This is also evident in Pompe disease: without an early diagnosis there is a progressive muscular and cardiac involvement with death in most of the cases within the first year of life, while in late-onset forms the course is slower, sneaky, with loss of walking mentation and the ability to breathe autonomously. An early diagnosis from neonatal screening allows starting therapy in the early days of life and monitoring in the late forms and then starting therapy when necessary allowing a normal life like peers ", said the Doctor Maria Alice Donati, Director of the Metabolic and Hereditary Muscle Diseases Unit of the Meyer Hospital in the city.  

"In Mucopolysaccharidosis type I (MPS I) there have been enormous therapeutic advances both in terms of drugs and in the practice of hematopoietic stem cell transplantation. In the Triveneto, thanks to the screening program we have identified two children, one had a transplant, two years old and is a perfectly normal child, the other is undergoing enzyme replacement therapy and is equally well: these children without screening today would be seriously compromised and perhaps still looking for a diagnosis. early management changes the natural history of these diseases, "explained the Prof. Alberto Burlina, Director of the UOC Metabolic Diseases Inheriting at the University Hospital of Padua.

The primitive immunodeficiele

Il Working table that assessed primary immunodeficiencies has divided them into two blocks,

  1. on the one hand the forms SCID or "severe combined immunodeficiency" (hence ADA Scid and PNP Scid),
  2. on the other, a group of "other Immunodeficiencies detectable with TREC / KREK type tests".

"Immunodeficiencies are serious diseases of the immune system, those affected have a lower ability to cope with viruses, fungi and bacteria and undergo very serious recurrent infections that can also lead to organ damage and early death. there is a diagnosis at birth it is possible to understand the cause of infections only after they occur, with sometimes fatal consequences, instead, screening allows us to act both with prophylaxis - reducing infections with the administration of immunoglobulins and antibiotics - that to set a therapy for the specific form early. In some cases it is possible to resort to donor transplantation of haematopoietic stem cells or, in the case of ADA Scid, also to gene therapy, which is an approved drug resulting from the research of Del Paesena ", said the Prof. Alessandro Aiuti, Deputy Director of the San Raffaele Telethon Institute for gene therapy. For the ADA Scid, but also for the less common PNP form and for the other forms of congenital immunodeficiencies, Tuscany is the first - and for now the only - Del Paesena region to carry out screening. From 2022 to date, 5 children have been diagnosed with Scid. In the light of these data, but also taking into account some differences between the tests needed for this screening, the working group expressed favorable opinion for the immediate inclusion of the ADA Scid in the screening panel, an insertion conditional to the CE marking of the diagnostic kit for PNP Scid and the insertion of the panel, but with deferred start, for all other immunodeficiencies, because laboratories will need time to adapt.

Metabolic diseases

The working group that evaluated the metabolic diseases instead he focused on a single pathology, given that about 40 had already been included in the 2022 list: only for Adrenoleukodystrophy, in its cerebral form (CALD), in fact, there have been such important changes as to induce the table to give without any doubt a favorable opinion for inclusion in the panel, as established also in the USA from 2022. This form presents with severe and progressively worsening neurological problems and begins around the 3-12 years. For the treatment of this pathology today it is possible to intervene with a hematopoietic stem cell transplant, which can only be performed with a compatible donor, but - and this is the latest news - gene therapy should be available very soon. Even from the point of view of the test, there are no particular difficulties or costs that should be incurred, to the point that Tuscany is also considering the launch of a screening pilot project. "Today most of the early diagnoses are made only thanks to innocent victims, brothers, cousins ​​who die opening long galleries of pain in the history of families. These victims lead to more in-depth investigations also to other relatives, so that they are not irremediably affected by the disease. . We hope not to see children dying prematurely to save the lives of other children, but to see the Health System take responsibility, to implement effective tools to ensure early diagnosis throughout the country and health policies that allow rapid access to the next advanced therapies, protecting the right to life of all newborns in the country ", he concluded Valentina Fasano, President of the AIALD Association that deals with this pathology.

Read also: Aicardi Goutieres syndrome what it is and how it is treated

  • test at screening
add a comment of Neonatal screening: at least 7 other diseases are to be added to the national list
Comment sent successfully! We will review it in the next few hours.