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

TITLE=Hereditary orotic aciduria identified by newborn screening

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1135267

DOI=10.3389/fgene.2023.1135267

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Methods:</bold> Measuring orotic acid as part of expanded newborn screening using flow injection analysis tandem mass spectrometry.</p><p><bold>Results:</bold> 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 <italic>UMPS</italic> gene.</p><p><bold>Conclusion:</bold> Newborn screening measuring of orotic acid, now integrated into the routine tandem mass spectrometry panel, is capable of identifying neonates with hereditary orotic aciduria.</p>