August 2016 saw the passing of Bill 167, envisaging that all newborns in Italy undergo free-of-charge Expanded Newborn Screening (ENS) few hours after birth. The test enables to early identify about 40 genetic metabolic disorders, difficult to diagnose yet easy to detect through ENS. Treatments and cures for such diseases already exist, and their early use during the first days after birth, before the symptoms are visible, can significantly increase a child's quality of life or even prevent death. At present, about 800 inherited metabolic disorders affecting metabolic biochemistry are known: about 40 of which can be early detected just a few days after birth.
Before Bill 167, a regional screening was performed on nearly all newborns in Italy to identify only three diseases: phenylketonuria (PKU), congenital hypothyroidism (CH) and cystic fibrosis (CF). There were few birth centres where children could undergo expanded screening: in 2015 only one child out of two underwent ENS for multiple metabolic disorders and the amount of disorders screened for changed according to the area. An unacceptable disparity with severe consequences for ill babies: the difference between life and death, between a good quality of life and disability. All Italian Regions have adapted, or are adapting to the regulation, hence coupling the regional screening panel with Expanded Newborn Screening (ENS). The hope is that within the first months of 2018 will see full coverage across the Italian territory and that all Birth Centres can screen about 40 disorders envisaged by the regulation (MD. 13-10-2016), hence enlisted in the official panel required by law.
Early identification of about 40 inherited metabolic disorders enlisted in the official panel means offering hope to survive and a better quality of life to an ill baby. This happens because such disorders are otherwise very difficult to detect since their onset includes a vast array of symptoms and/or they degenerate very quickly, in some cases even within a few hours. Early intervention through drugs and tailored diets can limit irreversible damages to the brain and organs which may lead to cognitive and physical disabilities that are often severe or even to the baby's death. Estimates indicate that 1 newborn out of 1,500 is affected by a disorder detectable through screening.
Between 48 and 72 hours after birth, or before the baby is homed from the Birth Centre, a small blood sample is taken from the baby's heel and then blotted and dried on filtered paper (Dried blood spot). The sample previously used to screen phenylketonuria, congenital hypothyroidism and cystic fibrosis (compulsory regional screening), is now used to screen 40 disorders. No further samples are then needed. The Birth Centre ships the sample to its regional or interregional reference Screening Centre with delivery within 24/48 hours. The Screening Centre shall analyse the sample on the arrival day or on the following day.
The screening centre does not communicate negative results, only positive risk profiles are contacted through the Birth Centre. Caution: positive results do not always mean there is a disorder. Test results can be positive due to the extreme sensitivity of the device used for the analysis or due to the way the test was performed. Premature birth of even just a few days, low birth weight, drug support and parenteral nutrition can all lead do positive test results. For premature newborns, babies with lower gestational weight, undergoing parenteral nutrition or homed before 48 hours of life, however, the blood sample has to be taken before homing, but it shall be repeated within the first month of life, according to scientific protocols and evidence. Do not be afraid then, serenely rely on your Birth Centre that will provide you with all the necessary information to continue your baby's health follow-up. If the test is positive, the protocol foresees that the baby is referred for follow-up care with varying time and mode according to the type of ‘suspected’ disorder. If the disorder requires immediate therapy, the parents shall be asked to bring the baby to the reference Clinical Centre to undergo a timely first treatment and to confirm the suspect diagnosis (patient management). If the disorder is not immediately degenerative, the baby can be referred for a second screening that may lead to a negative or positive result. If positivity is confirmed, the baby shall be monitored through one or two blood samples and in case of positive result the parents shall be asked to bring their baby to the reference Clinical Centre for treatment and diagnosis confirmation (patient management). To confirm the molecular genetic diagnosis of a hereditary metabolic disorder, the Clinical Centre collects the Parental informed consent (See informed consent sample). The confirmation of diagnosis for the disorder can take many weeks. Meanwhile, the baby shall receive all possible treatments for the disorder, including preemptive treatments. (See Diagnosis, certification, exemption, click here)
Ministerial Decree 13-10-2016 lists the pathologies included in the Expanded Newborn Screening panel, namely:
Deficit biosintesi cofattore biopterina
Deficit rigenerazione cofattore biopterina
Tirosinemia tipo I
Tirosinemia tipo II
Malattia delle urine allo sciroppo d’acero
Omocistinuria (deficit di CBS)
Acidemia glutarica tipo I
Deficit del Beta-chetotiolasi
Aciduria 3-Idrossi 3-metil glutarica
Acidemia Metilmalonica (Mut)
Acidemia Metilmalonica (CblA)
Acidemia Metilmalonica (CblB)
Acidemia Metilmalonica con Omocistinuria (CblC)
Acidemia Metilmalonica con Omocistinuria (CblD)
Deficit del 2-Metil butirril-CoA deidrogenasi
Deficit Multiplo delle carbossilasi
Citrullinemia tipo I
Citrullinemia tipo II (deficit di Citrina)
Deficit del trasporto della carnitina
Deficit di Carnitina palmitoil-transferasi (L)
Deficit Carnitina/acil-carnitina translocasi
Deficit di Carnitina palmitoil-transferasi II
Deficit dell’acil CoA deidrogenasi a catena molto lunga
Deficit della proteina trifunzionale
Deficit dell’idrossiacil CoA deidrogenasi a catena lunga
Deficit dell’acil CoA deidrogenasi a catena media
Deficit del 3-OH acil-CoA deidrogenasi a catena media/corta
Acidemia glutarica tipo II
Difetto di biotinidasi
Tirosinemia tipo III
Deficit di glicina N-metiltransferasi
Deficit di Metionina adenosiltransferasi
Deficit di S-adenosilomocisteina idrolasi
Acidurie 3-metil glutaconiche
Deficit del 3-Metil crotonil-CoA carbossialsi
Aciduria 2-Metil 3-idrossi butirrico
Deficit del Isobutirril-CoA deidrogenasi
Deficit dell’acil CoA deidrogenasi a catena corta
Some disorders have already been enlisted in many regional screening programmes and prevention has proven effective in case of: Congenital adrenal hyperplasia, some Lysosomal storage diseases, Severe combined immunodeficiency (SCID), GAMT deficiency, some Hemoglobinopathies. More shall soon be added, such as: X-linked adrenoleukodystrophy, Argininosuccinic aciduria, Ornithine transcarbamylase (OCT) deficiency, other Immunodeficiencies/trek. For such disorders, not yet included in the compulsory panel, the screening shall require the Parental informed consent. (See informed consent sample).
Parents should be aware that some disorders included in the official screening panel can also have a very early onset, within 3-5 days after the baby is born or a little later, according to the severity of the disorder (the same disorder may also have different degrees of severity). The disorder can, though quite rarely, have an onset before the test results are known (types of hyperammonemia and organic aciduria).
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