Rare Ophthalmology News

Disease Profile

Orotic aciduria type 1

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

E79.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Orotidylic pyrophosphorylase and orotidylic decarboxylase deficiency; UMPS deficiency; Uridine monophosphate synthase deficiency;

Categories

Blood Diseases; Congenital and Genetic Diseases; Metabolic disorders

Summary

Orotic aciduria type I (OA1), also known as hereditary orotic aciduria, is a rare condition characterized by elevated levels of orotic acid in the urine.[1] It typically becomes apparent in the first months of life with megaloblastic anemia, as well as delays in physical and intellectual development.[1][2] OA1 is caused by changes (mutations) in the UMPS gene and inheritance is autosomal recessive. OA1 differs from other causes of orotic aciduria, which may include mitochondrial disorders, lysinuric protein intolerance, and liver disease.[1]

Treatment involves taking uridine; uridine triacetate was granted FDA approval for treating OA1 in 2015.[3] Without treatment, children with OA1 may experience neutropenia, failure to thrive, developmental delay, and intellectual disability.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

0003355
Anemia
Low number of red blood cells or hemoglobin
0001903
Global developmental delay
0001263
Orotic acid crystalluria
0003526
Oroticaciduria
High urine orotic acid levels
0003218
30%-79% of people have these symptoms
Abnormal toenail morphology
Abnormality of the toenail
Abnormality of the toenails

[ more ]

0008388
Abnormality of the ureter
0000069
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Hip dysplasia
0001385
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Impaired T cell function
T-cell dysfunction
0005435
Low-set, posteriorly rotated ears
0000368
Patent ductus arteriosus
0001643
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Splenomegaly
Increased spleen size
0001744
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
5%-29% of people have these symptoms
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Percent of people who have these symptoms is not available through HPO
Anisocytosis
Unequal size of red blood cells
0011273
Autosomal recessive inheritance
0000007
Folate-unresponsive megaloblastic anemia
0004826
Hematuria
Blood in urine
0000790
Hypochromia
0032231
Poikilocytosis
0004447
Pyrimidine-responsive megaloblastic anemia
0003339
Reduced orotidine 5-prime phosphate decarboxylase level
0003267

Diagnosis

Orotic aciduria type I (OA1) is diagnosed by a urine test that reveals very high amounts of orotic acid, with milder elevations of orotidine. The respective amounts of these substances result in an OA/orotidine ratio of above 10.[4] Genetic testing of the UMPS gene is also available. A correct and timely diagnosis of OA1 is key to effective treatment for the condition.[1]

Treatment

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    In-Depth Information

    • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
    • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
    • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
    • PubMed is a searchable database of medical literature and lists journal articles that discuss Orotic aciduria type 1. Click on the link to view a sample search on this topic.

      References

      1. Wortmann SB, Chen MA, Colombo R, et al. Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences. J Inherit Metab Dis. May, 2017; 40(3):423-431. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393157/.
      2. Nyhan WL. Disorders of purine and pyrimidine metabolism. Molecular Genetics and Metabolism. 2005; 86:25-33. https://www.ncbi.nlm.nih.gov/pubmed/16176880. Accessed 4/2/2012.
      3. Rautio J, Karkkainen J, Sloan KB. Prodrugs – Recent approvals and a glimpse of the pipeline. European Journal of Pharmaceutical Sciences. November, 2017; 109:146-161. https://www.ncbi.nlm.nih.gov/pubmed/28782609.
      4. Balasubramaniam S, Duley JA, Christodoulou J. Inborn errors of pyrimidine metabolism: clinical update and therapy. J Inherit Metab Dis. September, 2014; 37(5):687-698. https://www.ncbi.nlm.nih.gov/pubmed/25030255.

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