Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation

Absi, Hebah S. Al; Sacharow, Stephanie; Zein, Naser Al; Shamsi, Aisha Al; Teneiji, Amal Al

doi:10.1016/j.ymgmr.2020.100703

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…The significance of orotic acid extends beyond its biological functions, as it has garnered attention for its potential therapeutic applications [25]. For example, orotic acid has been used in the treatment of some genetic disorders, such as hereditary orotic aciduria [26] and some forms of urea cycle disorders [24], as it can help improve the body's ability to produce and excrete urea. However, there is limited research on the use of orotic acid in cosmetics, and its potential benefits and drawbacks have not been well established.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study

Kim

Lee

Mun

et al. 2023

IJMS

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The present study investigated the effect of topical application of Epidermidibacterium Keratini (EPI-7) ferment filtrate, which is a postbiotic product of a novel actinobacteria, on skin aging, by performing a prospective randomized split-face clinical study on Asian woman participants. The investigators measured skin biophysical parameters, including skin barrier function, elasticity, and dermal density, and revealed that the application of the EPI-7 ferment filtrate-including test product resulted in significantly higher improvements in barrier function, skin elasticity, and dermal density compared to the placebo group. This study also investigated the influence of EPI-7 ferment filtrate on skin microbiome diversity to access its potential beneficial effects and safety. EPI-7 ferment filtrate increased the abundance of commensal microbes belonging to Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Clostridium, Rothia, Lactobacillus, and Prevotella. The abundance of Cutibacterium was significantly increased along with significant changes in Clostridium and Prevotella abundance. Therefore, EPI-7 postbiotics, which contain the metabolite called orotic acid, ameliorate the skin microbiota linked with the aging phenotype of the skin. This study provides preliminary evidence that postbiotic therapy may affect the signs of skin aging and microbial diversity. To confirm the positive effect of EPI-7 postbiotics and microbial interaction, additional clinical investigations and functional analyses are required.

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Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study

Kim

Lee

Mun

et al. 2023

IJMS

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“…To the best of our knowledge, this UMPS nonsynonymous mutation (c.517G>C) had never been identified in the single-nucleotide polymorphism database (dbSNP), Leiden Open Variation Database (LOVD) (v3.1), and ClinVar ( https://www.ncbi.nlm.nih.gov/clinvar/ ) databases. There are previous reports of patients with seizure-associated HOA ( 2 , 5 ), thus, proposing a link between UMPS deficiency and epilepsy. Intellectual disability occurs in patients with OA with homozygous and heterozygous UPMS mutations ( 1 ).…”

Section: Discussionmentioning

confidence: 93%

“…In 2015, the U.S. Food and Drug Administration approved a treatment for HOA called uridine triacetate (Xuriden), which is a pyrimidine analog indicated for uridine replacement therapy ( 7 ). Patients who took the drug responded well ( 5 ). Although our proband only took mecobalamin, he was seizure-free for one year.…”

Section: Discussionmentioning

confidence: 99%

Case Report: A Novel Missense Mutation c.517G>C in the UMPS Gene Associated With Mild Orotic Aciduria

Ma¹,

Ye²,

Han³

et al. 2022

Front. Neurol.

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BackgroundHereditary orotic aciduria (HOA) is a rare genetic disorder of pyrimidine metabolism caused by variations in the uridine monophosphate synthetase (UMPS) gene and inheritance are autosomal recessive. Heterozygous UMPS mutations can also lead to orotic aciduria without clinical consequence.MethodsWe conducted molecular genetic analyses on proband using whole-exome sequencing (WES) and on 12 family members using Sanger sequencing for UMPS mutation. We analyzed the urine metabolites of family members carrying UMPS heterozygous variants with standard gas chromatography-mass spectrometry (GC-MS).ResultsWe identified a novel UMPS mutation (c.517G>C) in a Chinese-origin of orotic aciduria pedigree. The proband presented with epilepsy and intellectual disability (ID). Other mutation carriers in our pedigree presented with mild orotic aciduria without relevant medical complaints except for the proband.ConclusionOur study further expanded the genotype of orotic aciduria and highlighted the probability of misdiagnosis in clinical practice.

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“…She presented with unexplained megaloblastic bone marrow, immunodeficiency in form of recurrent infections, epilepsy, developmental delay and crystalluria. The patient showed clinical, hematologic, and biochemical improvement after being treated with uridine triacetate ( Al Absi et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Hereditary orotic aciduria identified by newborn screening

et al. 2023

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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.

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Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation

Cited by 7 publications

References 8 publications

Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study

Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study

Case Report: A Novel Missense Mutation c.517G>C in the UMPS Gene Associated With Mild Orotic Aciduria

Hereditary orotic aciduria identified by newborn screening

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