Severe combined immunodeficiencies

The diagnosis of combined severe immunodeficiency (SCID) is very scary because it carries with it a high risk of morbidity and early mortality. Among the group of serious genetic diseases affecting the immune system: children with SCID appear healthy at birth but decease in the first months or years of life due to very serious infections, if appropriate therapy is not promptly performed. Unfortunately, the SCID is discovered only when the child already develops a serious infection.

In the past ten years, science has been making huge advances, and today these diseases can be treated completely with haematopoietic stem cell transplantation and in some cases with gene therapy. This, for example, is what happened in the case of ADA SCID, thanks to the gene therapy developed by researchers in the Telethon Institute of San Raffaele for Gene Therapy, it could give a new hope to many families and young patients.

The time factor makes a difference

The earlier the diagnosis, the higher the probability of success of the applied treatments (bone marrow transplant from a donor or gene therapy). Early intervention also translates into a reduction in socio-medical costs because the hospitalization period is shorter, and because it is possible for the young patient to recover already in the first years of life, with a reduced need for assistance.

Neonatal screening to protect the health of new-borns

Before being discharged from the hospital, under the Italian law, all new-born babies are subject

(Law RI 104/1992 and subsequent regional integrations) to undergo a capillary blood sampling for neonatal screening, that is performed by pricking the baby’s heel with a needle and collecting a few drops of blood that are used to complete several tests, useful for the early detection of some rare congenital diseases.

The evolution of neonatal screening has led to an extension of the tests in recent decades and today with the law 167/2016 "Provisions on the subject of mandatory neonatal diagnostic tests for the prevention and treatment of inherited metabolic diseases" the screening test is extended at 40 metabolic diseases. Thanks to this kind of test you can know, within a few hours of birth, if a new-born is suffering from a congenital metabolic disease for which treatment may be available that can change the natural history, avoiding serious complications. The introduction of an extended neonatal screening has marked a turning point: it has gone from the baseline screening for 3 pathologies (phenylketonuria, congenital hypothyroidism and cystic fibrosis) to screening for more than 40 pathologies. This profound change has also revolutionized the clinical history of the pathologies involved, which through an early diagnosis have finally found a tool for an effective treatment. However, in Italy not all regions perform extensive neonatal screening required by law, and only in a few other hospitals pilot projects are currently active, so today where we are born makes a difference.

As for the combined severe immunodeficiencies, several experimental neonatal screening tests are performed at the Meyer Hospital in Florence. For some of these, the pilot phase has already been completed, and the tests have recently been included among those mandatory for infants born in the Tuscany Region.

The pilot project at the IRCCS San Raffaele Hospital in Milan

From this year also in Milan, at the San Raffaele Hospital a pilot project is active, in collaboration with the Meyer Hospital-University Laboratory (Florence), which offers all the children who are born in the Hospital the possibility of performing experimental neonatal screening tests for the main forms of combined severe immunodeficiencies (SCID). A metabolic test is also performed for SCIDs caused by ADA or PNP defects. Through a small collection of drops of blood from the heel, additional to those used for the neonatal screening required by law, it is possible to identify the alterations responsible for these diseases. Early diagnosis is essential because it allows prompt application of the available treatment options, optimizing the effects on the patient's quality of life and reducing the associated health and social costs.

«It is important to widen the neonatal screening to those diseases that today have a cure like the ADA-SCID because we can immediately protect children from infections and intervene before serious damage occurs», Professor Alessandro Aiuti, Deputy Director of San Raffaele Telethon Institute for Gene Therapy and Head of the Paediatric Immunohematology Unit of the San Raffaele Hospital.

"We hope that this opportunity, which we can now offer to the newborns of San Raffaele thanks to the experimental project funded by the Ministry of Health, will soon become clinical practice, with a mandatory test available throughout Italy", explains Dr. Graziano Barera, Head of the Neonatology Unit and Paediatrics of the San Raffaele Hospital.

The Neonatal screening in practice

Neonatal screening is a process that takes place in hospitals shortly before the baby's discharge and consists in collecting a few drops of blood from the baby's heel. This usually takes place between 48 and 72 hours after birth. The blood sample is absorbed on a special paper to obtain the so-called "dried blood spot on paper", which is sent to the reference Neonatal Screening Center. Together with the blood, the Center is provided with all the information necessary to identify the newborn, including parental data, their telephone and postal address, and any other information useful for conducting the tests.


The sample is then subjected to the necessary tests: if they are positive and therefore the presence of one of these diseases is suspected, the new-born will be invited back for further checks and for an evaluation by the clinical specialist. Screening tests do not give the certainty of the presence of a disease, they are not "diagnostic", but may indicate an increased risk that the child is affected

from one of the diseases being screened. A recall does not therefore mean that the child is ill, in many cases the alteration initially found can be transitory, and the child is healthy. There are also special conditions such as the use of medical devices, presence of maternal pathologies or neonatal pathologies, independent of the diseases being screened, which can cause false positives to screening tests.

As a rule, the Screening Center does not communicate to parents the results of the examination when there is no risk of illness: in the absence of communication in the first month of life, we can presume the absence of the disease. However, parents who wish to do so can contact the Center

of Screening or with the Birth Center to get information about the arrival, the state of progress of the sample processing and the test result.


Date: 19/05/2019

By: Gea Gardini

Translation and editing: Violetta Valeeva