by Health Editor
Thanks to the constant expansion of the panel of metabolic diseases tested at birth and the development of increasingly personalized therapies, in Italy today it is possible to detect over 40 metabolic defects at birth.
There are over a thousand hereditary metabolic diseases known and diagnosed and they belong to the group of rare diseases. This type of pathology can affect a total of about 1 new born every 2,000. Several of these pathologies have a highly disabling impact, which can in many cases be averted if recognition takes place at birth. This is possible thanks to the newborn screening of which International New Born Screening Day is celebrated on 28 June. The date was chosen because it was the birthday of Robert Guthrie, a microbiologist to microbiologist who first proposed the use of newborn screening for phenylketonuria (see below).
What is newborn screening?
Newborn screening is performed by taking a few drops of blood from the newborn’s heel at the point of birth between 48 and 72 hours of life. The sample is sent to a reference laboratory, where the concentration in the blood of substances (metabolites) is measured, the alteration of which indicates the presence of specific diseases. If an alteration is detected, further diagnostic tests are carried out to confirm the suspicion of the disease. Once the diagnosis has been made, the patient is entrusted to the Reference Centers of the National Rare Disease Network, to promptly start the specific treatment and follow up. Neonatal screening therefore represents one of the most important measures for the prevention of congenital diseases, and is part of a complex system of care that involves patients, clinicians, families and associations.
What are hereditary metabolic diseases
“Hereditary metabolic diseases can be divided into two main macro-groups – explains Marco Spada, director of the complex structure of Pediatrics at the Regina Margherita Children’s Hospital – Città della Salute University Hospital of Turin and professor of Pediatrics at the University of Turin — both linked to a basic defect in the production of enzymes: in the first group, the enzymatic defect causes an overproduction of toxic substances that damage the organs, in the second group we find metabolic diseases in which the enzymatic defect causes a serious shortage of useful substances for the development. The therapeutic approach, depending on the case, will be to reduce the production of toxic substances or to integrate those substances that are not produced correctly, but the timeliness of the diagnosis is essential, since it is necessary to intervene with enzymatic, genetic and cellular therapies before the accumulation of complex molecules in the brain or body damages the organs. This is why newborn screening is the key element capable of improving the prognosis and quality of life of patients with metabolic diseases”. «Around 40 million newborns are screened each year for potentially lethal diseases in 110 countries – explains Clara Attia, Managing Director Southern Europe of Revvity, which provides tests and tools for screening – including phenylketonuria, congenital hypothyroidism, cystic fibrosis , spinal muscular atrophy (SMA), severe combined immunodeficiency (SCID), and Duchenne muscular dystrophy (DMD). «The pediatric community today is particularly focused on four new groups of metabolic diseases: lysosomal diseases, chronic progressive diseases that cause multi-visceral organ damage that can be treated if promptly treated, neurodegenerative diseases, in which the target organ is the central nervous system, treatable with cell and gene therapies in the first months of life, neuromuscular diseases (such as spinal muscular atrophy or SMA, which causes death in the first year due to motor neuron defects) manageable with gene therapy and congenital immunodeficiencies, which expose children to sometimes lethal infections in the first months of life»
The history of newborn screening in Italy
In 1992, the Framework Law of 5 February 1992, n. 104 gave way to the first mandatory and free screening projects in some Italian regions. Initially it was possible to look for alterations related to only three diseases: congenital hypothyroidism, cystic fibrosis and phenylketonuria. During the 1990s it was progressively possible to extend newborn screening to a wider spectrum of rare diseases to arrive at what is called Extended Neonatal Screening – SN. With the Law of 19 August 2016, n. 167, Extended Neonatal Screening for metabolic diseases has been included in the LEA, Essential Levels of Assistance, guaranteeing mandatory and free screening extended to newborns throughout the national territory. To ensure further uniformity to the screening system with the Decree n. 33 of 9 March 2017 of the Director General of the Istituto Superiore di Sanità (ISS), the Neonatal Screening Coordination Center (CCSN) was established, which provides for collaboration between the Ministry of Health, representatives of the State – Regions Conference, clinicians with experience specific medical-scientific and representatives of patient associations. “With the introduction of the first newborn screening programs – underlines Spada – it was possible to identify in particular patients suffering from phenylketonuria and hypothyroidism from birth and this made it possible to completely eradicate two important causes of mental retardation in children. These diseases, in fact, if diagnosed promptly, can be treated thanks to specific diets or therapies, substantially modifying the patient’s prognosis. The 2016/17 law made Italy the first country in the world to introduce mandatory newborn screening for all newborns and together with the expansion of the panel from 3 diseases to over 40 that are being tested today, it gave us the tools to save every year in Italy many dozens of newborns from serious complications due to the late diagnosis of metabolic diseases, such as cognitive delays, sudden death, liver failure, coma, neurological degeneration, cardiomyopathies and many others”. The 2019 Budget Law (art.1 c.544) included genetic neuromuscular diseases, severe congenital immunodeficiencies and lysosomal storage diseases in the screening. In 2020, the Extended Neonatal Screening Working Group (SNE) was set up at the Ministry of Health, with the task of establishing the operational protocols for diagnosing and taking care of patients. With the Law of 10 November 2021 n. 175, the Consolidated Text on rare diseases was born, which introduced important provisions to guarantee complete and continuous assistance throughout the national territory for patients with rare diseases, as well as defining support for research and the production of special drugs intended for therapies. The system for dealing effectively with metabolic diseases involves families, clinicians, laboratories, public health and is a complex multidisciplinary process that starts in the very first stages of the child’s life and requires advanced diagnostic and organizational knowledge, in which the collaboration of different facilities and professionalism. A complex machine which in Italy, however, places us at the forefront not only in Europe, where we are the first country for the quantity of metabolic diseases tested on newborns, but also in the world, where we are second only to the United States.
The therapies
«Once the diagnosis has been clarified, depending on the type of chemical dynamics of the specific disease, we can act on the substrate, through diets and drugs that block the production of toxic metabolites or by integrating the deficient molecules. The other road we can take is that of enzymatic therapies. They work in different ways: we can supply the non-produced enzymes from the outside or stimulate the enzymatic production which is defective to bring it to 100%, or introduce hematopoietic stem cells through bone marrow or liver transplantation to allow the recipient to have the cells capable to produce the missing enzymes. Gene therapy, on the other hand, conveys new genetic information to the subject via viral vectors, which in this way begins to produce the missing enzyme. Today we can treat previously incurable situations, combining the increased diagnostic capacity provided by tests capable of finding metabolites in the blood at birth with the development of increasingly effective new therapies”. “That’s why – concludes Spada – if the legislative process works, it will lead us to increase the panel of diagnosed pathologies every year”.
June 27, 2023 (change June 27, 2023 | 20:27)
© breaking latest news