Early-Onset Inherited Metabolic Diseases: When Clinical Symptoms Precede Newborn Screening—Insights from Emilia-Romagna (Italy)
Background: Expanded Newborn Screening (ENS) allows the early identification of many inherited metabolic diseases (IMDs) for which timely treatment can modify the natural history. For most IMDs, diagnosis by ENS is pre-clinical. However, clinical symptoms may emerge for certain conditions before scr...
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MDPI AG
2025-04-01
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| author | Giulia Montanari Egidio Candela Federico Baronio Vittorio Ferrari Giacomo Biasucci Marcello Lanari Rita Ortolano |
| author_facet | Giulia Montanari Egidio Candela Federico Baronio Vittorio Ferrari Giacomo Biasucci Marcello Lanari Rita Ortolano |
| author_sort | Giulia Montanari |
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| description | Background: Expanded Newborn Screening (ENS) allows the early identification of many inherited metabolic diseases (IMDs) for which timely treatment can modify the natural history. For most IMDs, diagnosis by ENS is pre-clinical. However, clinical symptoms may emerge for certain conditions before screening results become available. Methods: We describe six cases of patients with early-onset IMDs born between 2013 and 2023, who were admitted or transferred to Sant’Orsola University Hospital in Bologna (Italy). Results: Over the study period, 379,013 newborns underwent ENS in the Italian region of Emilia-Romagna. Excluding cases of congenital hypothyroidism, pre-clinical diagnoses from ENS were 410. In addition, six cases of IMD presented with early-onset clinical symptomatology, an antecedent to the outcome of newborn screening (incidence over 11 years of 1.58 cases per 100,000 infants). Among these patients, three were diagnosed with Urea Cycle Disorders (UCDs)—two with Citrullinemia type I (CIT1) and one with Argininosuccinic Acidemia (ASA); two were diagnosed with Methylmalonic Acidemia (MMA); and one was found to have Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD). Conclusions: Our 11-year experience with ENS has shown that clinical onset can occur between the second and fourth day of life, though rare. Even if dried blood spot (DBS) collection was performed 24–48 h after birth, the time required for sample transportation and processing would still delay result availability, making early intervention unlikely. Therefore, our experience supports performing ENS at 48–72 h, as currently implemented in Italy, while also highlighting the advantages and limitations of earlier screening. |
| format | Article |
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| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Children |
| spelling | doaj-art-91edb8a7ade3482c9e8c5dd7dd3a2c1c2025-08-20T02:17:24ZengMDPI AGChildren2227-90672025-04-0112446410.3390/children12040464Early-Onset Inherited Metabolic Diseases: When Clinical Symptoms Precede Newborn Screening—Insights from Emilia-Romagna (Italy)Giulia Montanari0Egidio Candela1Federico Baronio2Vittorio Ferrari3Giacomo Biasucci4Marcello Lanari5Rita Ortolano6Specialty School of Pediatrics, Alma Mater Studiorum, University of Bologna, 40126 Bologna, ItalyPediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyPediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalySpecialty School of Pediatrics, Alma Mater Studiorum, University of Bologna, 40126 Bologna, ItalyPediatrics and Neonatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, ItalyPediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyPediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyBackground: Expanded Newborn Screening (ENS) allows the early identification of many inherited metabolic diseases (IMDs) for which timely treatment can modify the natural history. For most IMDs, diagnosis by ENS is pre-clinical. However, clinical symptoms may emerge for certain conditions before screening results become available. Methods: We describe six cases of patients with early-onset IMDs born between 2013 and 2023, who were admitted or transferred to Sant’Orsola University Hospital in Bologna (Italy). Results: Over the study period, 379,013 newborns underwent ENS in the Italian region of Emilia-Romagna. Excluding cases of congenital hypothyroidism, pre-clinical diagnoses from ENS were 410. In addition, six cases of IMD presented with early-onset clinical symptomatology, an antecedent to the outcome of newborn screening (incidence over 11 years of 1.58 cases per 100,000 infants). Among these patients, three were diagnosed with Urea Cycle Disorders (UCDs)—two with Citrullinemia type I (CIT1) and one with Argininosuccinic Acidemia (ASA); two were diagnosed with Methylmalonic Acidemia (MMA); and one was found to have Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD). Conclusions: Our 11-year experience with ENS has shown that clinical onset can occur between the second and fourth day of life, though rare. Even if dried blood spot (DBS) collection was performed 24–48 h after birth, the time required for sample transportation and processing would still delay result availability, making early intervention unlikely. Therefore, our experience supports performing ENS at 48–72 h, as currently implemented in Italy, while also highlighting the advantages and limitations of earlier screening.https://www.mdpi.com/2227-9067/12/4/464expanded newborn screeningearly-onset metabolic disorderstiming of screeningurea cycle disordersorganic acidemiasfatty acid oxidation disorders |
| spellingShingle | Giulia Montanari Egidio Candela Federico Baronio Vittorio Ferrari Giacomo Biasucci Marcello Lanari Rita Ortolano Early-Onset Inherited Metabolic Diseases: When Clinical Symptoms Precede Newborn Screening—Insights from Emilia-Romagna (Italy) Children expanded newborn screening early-onset metabolic disorders timing of screening urea cycle disorders organic acidemias fatty acid oxidation disorders |
| title | Early-Onset Inherited Metabolic Diseases: When Clinical Symptoms Precede Newborn Screening—Insights from Emilia-Romagna (Italy) |
| title_full | Early-Onset Inherited Metabolic Diseases: When Clinical Symptoms Precede Newborn Screening—Insights from Emilia-Romagna (Italy) |
| title_fullStr | Early-Onset Inherited Metabolic Diseases: When Clinical Symptoms Precede Newborn Screening—Insights from Emilia-Romagna (Italy) |
| title_full_unstemmed | Early-Onset Inherited Metabolic Diseases: When Clinical Symptoms Precede Newborn Screening—Insights from Emilia-Romagna (Italy) |
| title_short | Early-Onset Inherited Metabolic Diseases: When Clinical Symptoms Precede Newborn Screening—Insights from Emilia-Romagna (Italy) |
| title_sort | early onset inherited metabolic diseases when clinical symptoms precede newborn screening insights from emilia romagna italy |
| topic | expanded newborn screening early-onset metabolic disorders timing of screening urea cycle disorders organic acidemias fatty acid oxidation disorders |
| url | https://www.mdpi.com/2227-9067/12/4/464 |
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