Frontiers in Genetics (Mar 2023)
Hereditary orotic aciduria identified by newborn screening
- Orna Staretz-Chacham,
- Orna Staretz-Chacham,
- Orna Staretz-Chacham,
- Nadirah S. Damseh,
- Suha Daas,
- Nasser Abu Salah,
- Nasser Abu Salah,
- Yair Anikster,
- Yair Anikster,
- Ortal Barel,
- Elena Dumin,
- Elena Dumin,
- Aviva Fattal-Valevski,
- Aviva Fattal-Valevski,
- Tzipora C. Falik-Zaccai,
- Tzipora C. Falik-Zaccai,
- Eli Hershkovitz,
- Eli Hershkovitz,
- Eli Hershkovitz,
- Sagi Josefsberg,
- Yuval Landau,
- Yuval Landau,
- Tally Lerman-Sagie,
- Tally Lerman-Sagie,
- Hanna Mandel,
- Rachel Rock,
- Nira Rostami,
- Talya Saraf-Levy,
- Nava Shaul Lotan,
- Ronen Spiegel,
- Ronen Spiegel,
- Ronen Spiegel,
- Galit Tal,
- Galit Tal,
- Igor Ulanovsky,
- Yael Wilnai,
- Stanley H. Korman,
- Stanley H. Korman,
- Shlomo Almashanu
Affiliations
- Orna Staretz-Chacham
- Metabolic Clinic, Pediatric Division, Soroka University Medical Center, Ben Gurion University, Beer- Sheva, Israel
- Orna Staretz-Chacham
- Faculty of Health Sciences, Ben-Gurion University, Beer Sheva, Israel
- Orna Staretz-Chacham
- Institute for Rare Diseases, Soroka University Medical Center, Ben Gurion University, Beer- Sheva, Israel
- Nadirah S. Damseh
- Faculty of Medicine, Al-Quds University, Palestinian National Authority, Abu Deis, Palestine
- Suha Daas
- National Newborn Screening Program, Public Health Services, Ministry of Health, Ramat-Gan, Israel
- Nasser Abu Salah
- Department of Neonatology, Red Crescent Society Hospital, Jerusalem, Israel
- Nasser Abu Salah
- School of Medicine, Hebrew University School of Medicine, Jerusalem, Israel
- Yair Anikster
- Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
- Yair Anikster
- Metabolic Disease Unit, Sheba Medical Center Tel-Hashomer, Edmond and Lily Safra Children’s Hospital, Ramat Gan, Israel
- Ortal Barel
- 0Genomics Unit, The Center for Cancer Research, Sheba Medical Center, Ramat Gan, Israel
- Elena Dumin
- 1Metabolic Laboratory, Sheba Medical Center, Ramat Gan, Israel
- Elena Dumin
- 2Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Aviva Fattal-Valevski
- 3Tel Aviv Sourasky Medical Center, Dana Children Hospital, Pediatric Neurology Institute, Tel Aviv, Israel
- Aviva Fattal-Valevski
- Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
- Tzipora C. Falik-Zaccai
- 4Galilee Medical Center, Institute of Human Genetics, Naharia, Israel
- Tzipora C. Falik-Zaccai
- 5The Azrieli Faculty of Medicine, Bar Ilan, Safed, Israel
- Eli Hershkovitz
- Metabolic Clinic, Pediatric Division, Soroka University Medical Center, Ben Gurion University, Beer- Sheva, Israel
- Eli Hershkovitz
- Faculty of Health Sciences, Ben-Gurion University, Beer Sheva, Israel
- Eli Hershkovitz
- 6Pediatric D Department, Soroka Medical Center, Beer Sheva, Israel
- Sagi Josefsberg
- 7Kaplan Medical Center, Genetics Institute, Rehovot, Israel
- Yuval Landau
- 8Metabolic Disease Unit, Schneider Children’s Medical Center, Petah Tikva, Israel
- Yuval Landau
- Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
- Tally Lerman-Sagie
- 9Magen Center for Rare Diseases-Metabolic, Neurogenetic, Wolfson Medical Center, Holon, Israel
- Tally Lerman-Sagie
- Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
- Hanna Mandel
- 0Metabolic Unit, Department of Genetics, Rebecca Sieff Hospital, Safed, Israel
- Rachel Rock
- National Newborn Screening Program, Public Health Services, Ministry of Health, Ramat-Gan, Israel
- Nira Rostami
- National Newborn Screening Program, Public Health Services, Ministry of Health, Ramat-Gan, Israel
- Talya Saraf-Levy
- National Newborn Screening Program, Public Health Services, Ministry of Health, Ramat-Gan, Israel
- Nava Shaul Lotan
- 1Department of Genetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- Ronen Spiegel
- 2Department of Pediatrics B, Metabolic Service, Emek Medical Center, Afula, Israel
- Ronen Spiegel
- 3Emek Medical Center, Institute for Rare Diseases, Afula, Israel
- Ronen Spiegel
- 2Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Galit Tal
- 4Rambam Medical Center, Metabolic Clinic, Ruth Rappaport Children’s Hospital, Haifa, Israel
- Galit Tal
- 2Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Igor Ulanovsky
- National Newborn Screening Program, Public Health Services, Ministry of Health, Ramat-Gan, Israel
- Yael Wilnai
- 5Tel Aviv Sourasky Medical Center, Genetic Institute, Tel Aviv, Israel
- Stanley H. Korman
- 4Rambam Medical Center, Metabolic Clinic, Ruth Rappaport Children’s Hospital, Haifa, Israel
- Stanley H. Korman
- 6Shaare Zedek Medical Center, Wilf Children’s Hospital, Jerusalem, Israel
- Shlomo Almashanu
- National Newborn Screening Program, Public Health Services, Ministry of Health, Ramat-Gan, Israel
- DOI
- https://doi.org/10.3389/fgene.2023.1135267
- Journal volume & issue
-
Vol. 14
Abstract
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.
Keywords
- newborn screening (NBS)
- hereditary orotic aciduria
- uridine monophosphate synthase
- orotic acid
- megaloblastic anemia
- neurodevelopmental disability
