Newborn screening algorithm distinguishing potential symptomatic isovaleric acidemia from asymptomatic newborns.

Autor: Rock R; National Newborn Screening Program, Ministry of Health, Tel-HaShomer, Ramat-Gan, Israel.; Metabolic Diseases Clinic, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-HaShomer, Israel., Rock O; Department of Ophthalmology, Sheba Medical Center, Tel-HaShomer, Israel.; Faculty of Medicine and Health Sciences, Tel Aviv University, Tel-Aviv, Israel., Daas S; National Newborn Screening Program, Ministry of Health, Tel-HaShomer, Ramat-Gan, Israel., Biton-Regev V; National Newborn Screening Program, Ministry of Health, Tel-HaShomer, Ramat-Gan, Israel., Sagiv N; National Newborn Screening Program, Ministry of Health, Tel-HaShomer, Ramat-Gan, Israel., Salah NA; Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel.; Department of Neonatology, Red Crescent Society Hospital, Jerusalem, Israel., Anikster Y; Faculty of Medicine and Health Sciences, Tel Aviv University, Tel-Aviv, Israel.; Edmond and Lily Safra Children's Hospital Sheba Medical Center, Tel-HaShomer, Ramat Gan, Israel., Barel O; Genomics Unit, The Center for Cancer Research, Sheba Medical Center, Tel-HaShomer, Ramat Gan, Israel., Cohen RH; Pediatric Neurology Unit and Magen Rare Disease Center, Wolfson Medical Center, Holon, Israel., Dumin E; Clinical Metabolic Laboratory, Sheba Medical Center, Tel-HaShomer, Ramat Gan, Israel.; Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Fattal-Valevski A; Faculty of Medicine and Health Sciences, Tel Aviv University, Tel-Aviv, Israel.; Pediatric Neurology Unit, Dana Children Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel., Falik-Zaccai T; Institute of Human Genetics, The Galilee Medical Center, Naharia, Israel.; The Azrieli Faculty of Medicine, Bar Ilan, Israel., Herskovitz E; Pediatric D Department, Soroka Medical Center, Beer Sheva, Israel.; Faculty of Health Sciences, Ben-Gurion University, Beer Sheva, Israel., Josefsberg S; Genetics Institute, Kaplan Medical Center, Rehovot, Israel., Khammash H; Department of Neonatology, Makassed Islamic Hospital, Jerusalem, Israel., Kneller K; Metabolic Diseases Clinic, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-HaShomer, Israel., Korman SH; Wilf Children's Hospital, Shaare Zedek Medical Center, Jerusalem, Israel.; Metabolic Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel., Landau YE; Faculty of Medicine and Health Sciences, Tel Aviv University, Tel-Aviv, Israel.; Metabolic Disease Unit, Schneider Children's Medical Center of Israel, Tel Aviv University, Israel., Lerman-Sagie T; Faculty of Medicine and Health Sciences, Tel Aviv University, Tel-Aviv, Israel.; Pediatric Neurology Unit and Magen Rare Disease Center, Wolfson Medical Center, Holon, Israel., Mandel H; Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.; Metabolic Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel., Pras E; Faculty of Medicine and Health Sciences, Tel Aviv University, Tel-Aviv, Israel.; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan, Israel., Reznik-Wolf H; The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan, Israel., Shaag A; Department of Genetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel., Lotan NS; Department of Genetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel., Spiegel R; Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.; Department of Pediatrics B, Metabolic Service, Emek Medical Center, Afula, Israel., Tal G; Metabolic Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel., Staretz-Chacham O; Metabolic Clinic, Pediatric Division, Soroka University Medical Center, Ben Gurion University, Beer-Sheva, Israel., Wilnai Y; Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel., Almashanu S; National Newborn Screening Program, Ministry of Health, Tel-HaShomer, Ramat-Gan, Israel.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2025 Jan; Vol. 48 (1), pp. e12800. Date of Electronic Publication: 2024 Sep 24.
DOI: 10.1002/jimd.12800
Abstrakt: Newborn screening (NBS) for isovaleric acidemia (IVA) reduces mortality and morbidity; however, it has also resulted in the detection of individuals with an asymptomatic or mild presentation for which early detection via newborn screening has not been proven to alter neurological outcome. We reevaluated biochemical and molecular data for newborns flagged positive for IVA in aim of developing a new screening algorithm to exclude the latter from positive screening. Among 2 794 365 newborns underwent routine newborn screening in Israel, 412 flagged positive for IVA, of which, 371 were false positives on recall sample testing and 41 positive newborns were referred to the clinic. 38/41 have biochemical and molecular confirmation in keeping with IVA. Among the 38 patients, 32% (12/38) were classified as symptomatic while, 68% (26/38) were classified as asymptomatic. 69% of the latter group harbor the known variant associated with mild potentially asymptomatic phenotype, c.932C>T; p. Ala311Val. Among asymptomatic patients, only 46% (12/26) are currently treated. Two novel variants have been detected in the IVD gene: c.487G>A; p. Ala163Thr and c.985A>G; p. Met329Val. Cut-off recalculation, of referred newborns' initial biochemical results, after classifying the referred patients to two binary groups of symptomatic and asymptomatic, resulted in an improved NBS algorithm comprising of C5 >5 μM and C5/C2>0.2 and C5/C3>4 flagging only those likely to have the classic symptomatic phenotype.
(© 2024 SSIEM.)
Databáze: MEDLINE
Externí odkaz: