Hereditary orotic aciduria identified by newborn screening

Orna Staretz-Chacham, Nadirah S. Damseh, Suha Daas, Nasser Abu Salah, Yair Anikster, Ortal Barel, Elena Dumin, Aviva Fattal-Valevski, Tzipora C. Falik-Zaccai, Eli Hershkovitz, Sagi Josefsberg, Yuval Landau, Tally Lerman-Sagie, Hanna Mandel, Rachel Rock, Nira Rostami, Talya Saraf-Levy, Nava Shaul Lotan, Ronen Spiegel, Galit TalIgor Ulanovsky, Yael Wilnai, Stanley H. Korman, Shlomo Almashanu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number1135267
JournalFrontiers in Genetics
Volume14
DOIs
StatePublished - 2023

Bibliographical note

Publisher Copyright:
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.

Keywords

  • hereditary orotic aciduria
  • megaloblastic anemia
  • neurodevelopmental disability
  • newborn screening (NBS)
  • orotic acid
  • uridine monophosphate synthase

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