Hereditary orotic aciduria identified by newborn screening

Frontiers in Genetics

Genetics

Nava Shaul Lotan¹  Nasser Abu Salah²  Ronen Spiegel³  Nadirah S. Damseh⁴  Tzipora C. Falik-Zaccai⁵  Ortal Barel⁶  Sagi Josefsberg⁷  Tally Lerman-Sagie⁸  Orna Staretz-Chacham⁹  Eli Hershkovitz^1,10  Yuval Landau^1,11  Elena Dumin^1,12  Hanna Mandel^1,13  Rachel Rock^1,14  Talya Saraf-Levy^1,14  Shlomo Almashanu^1,14  Nira Rostami^1,14  Suha Daas^1,14  Igor Ulanovsky^1,14  Galit Tal^1,15  Stanley H. Korman^1,16  Yair Anikster^1,17  Aviva Fattal-Valevski^1,18  Yael Wilnai^1,19 

[1] Department of Genetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;Department of Neonatology, Red Crescent Society Hospital, Jerusalem, Israel;School of Medicine, Hebrew University School of Medicine, Jerusalem, Israel;Department of Pediatrics B, Metabolic Service, Emek Medical Center, Afula, Israel;Emek Medical Center, Institute for Rare Diseases, Afula, Israel;Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel;Faculty of Medicine, Al-Quds University, Palestinian National Authority, Abu Deis, Palestine;Galilee Medical Center, Institute of Human Genetics, Naharia, Israel;The Azrieli Faculty of Medicine, Bar Ilan, Safed, Israel;Genomics Unit, The Center for Cancer Research, Sheba Medical Center, Ramat Gan, Israel;Kaplan Medical Center, Genetics Institute, Rehovot, Israel;Magen Center for Rare Diseases-Metabolic, Neurogenetic, Wolfson Medical Center, Holon, Israel;Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel;Metabolic Clinic, Pediatric Division, Soroka University Medical Center, Ben Gurion University, Beer- Sheva, Israel;Faculty of Health Sciences, Ben-Gurion University, Beer Sheva, Israel;Institute for Rare Diseases, Soroka University Medical Center, Ben Gurion University, Beer- Sheva, Israel;Metabolic Clinic, Pediatric Division, Soroka University Medical Center, Ben Gurion University, Beer- Sheva, Israel;Faculty of Health Sciences, Ben-Gurion University, Beer Sheva, Israel;Pediatric D Department, Soroka Medical Center, Beer Sheva, Israel;Metabolic Disease Unit, Schneider Children’s Medical Center, Petah Tikva, Israel;Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel;Metabolic Laboratory, Sheba Medical Center, Ramat Gan, Israel;Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel;Metabolic Unit, Department of Genetics, Rebecca Sieff Hospital, Safed, Israel;National Newborn Screening Program, Public Health Services, Ministry of Health, Ramat-Gan, Israel;Rambam Medical Center, Metabolic Clinic, Ruth Rappaport Children’s Hospital, Haifa, Israel;Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel;Rambam Medical Center, Metabolic Clinic, Ruth Rappaport Children’s Hospital, Haifa, Israel;Shaare Zedek Medical Center, Wilf Children’s Hospital, Jerusalem, Israel;Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel;Metabolic Disease Unit, Sheba Medical Center Tel-Hashomer, Edmond and Lily Safra Children’s Hospital, Ramat Gan, Israel;Tel Aviv Sourasky Medical Center, Dana Children Hospital, Pediatric Neurology Institute, Tel Aviv, Israel;Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel;Tel Aviv Sourasky Medical Center, Genetic Institute, Tel Aviv, Israel;

关键词: newborn screening (NBS);    hereditary orotic aciduria;    uridine monophosphate synthase;    orotic acid;    megaloblastic anemia;    neurodevelopmental disability;   

DOI  :  10.3389/fgene.2023.1135267

 received in 2022-12-31, accepted in 2023-02-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Hereditary orotic aciduria is an extremely rare, autosomal recessive disease caused by deficiency of uridine monophosphate synthase. Untreated, affected individuals may develop refractory megaloblastic anemia, neurodevelopmental disabilities, and crystalluria. Newborn screening has the potential to identify and enable treatment of affected individuals before they become significantly ill.Methods: Measuring orotic acid as part of expanded newborn screening using flow injection analysis tandem mass spectrometry.Results: Since the addition of orotic acid measurement to the Israeli routine newborn screening program, 1,492,439 neonates have been screened. The screen has identified ten Muslim Arab newborns that remain asymptomatic so far, with DBS orotic acid elevated up to 10 times the upper reference limit. Urine organic acid testing confirmed the presence of orotic aciduria along with homozygous variations in the UMPS gene.Conclusion: Newborn screening measuring of orotic acid, now integrated into the routine tandem mass spectrometry panel, is capable of identifying neonates with hereditary orotic aciduria.

【 授权许可】

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Copyright © 2023 Staretz-Chacham, Damseh, Daas, Abu Salah, Anikster, Barel, Dumin, Fattal-Valevski, Falik-Zaccai, Hershkovitz, Josefsberg, Landau, Lerman-Sagie, Mandel, Rock, Rostami, Saraf-Levy, Shaul Lotan, Spiegel, Tal, Ulanovsky, Wilnai, Korman and Almashanu.