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Orotic Aciduria via the UMPS Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
UMPS 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8437UMPS81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Hereditary orotic aciduria (MIM #258900) is a rare disorder of pyrimidine metabolism characterized by increased excretion of orotic acid in the urine, failure to thrive, and megaloblastic anemia. Hemoglobin levels often are in the 7-8 g/dL range, with hematocrit around 25% (Nyhan et al., 2012). This anemia is unresponsive to supplementation with iron, folate, or vitamin B12 (Huguley et al., 1959). Neutropenia is also present in most patients, with associated increased risk for infections. In the classical presentation, hair is sparse, fine, and very short; nail growth may also be poor. Some patients have been reported to have congenital anomalies, including cardiac malformations and strabismus (Van Kuilenburg et al., 2012).

Orotic acid crystals may be visualized in the urine via microscopy, and crystalluria may lead to gross or microscopic hematuria (Nyhan et al., 2012). The amount of orotic acid excreted by affected infants may be as high as 1000 times the normal adult mean, while orotidine excretion may also be elevated, but markedly less so (Sumi et al., 1997). Activities of aspartate transcarbamylase and dihydroorotase, two enzymes which occur earlier in the biochemical pathway, are also usually elevated.

Orotic aciduria represents pyrimidine nucleotide starvation in man. Impaired intellectual development has been observed in some patients. However, treatment in the form of oral uridine supplementation allows for remission (Nyhan et al., 2012; Van Kuilenburg et al., 2012). Dietary therapy leads to hematologic response, weight gain, increased activity levels, and improvement in overall well-being.


Hereditary orotic aciduria is caused by deficiency of uridine monophosphate (UMP) synthase. This enzyme is bifunctional in nature and catalyzes the last two steps in the de novo pyrimidine biosynthetic pathway. The enzyme’s two independent catalytic activities include orotate phosphoribosyltransferase (OPRT), which converts orotic acid to orotidine-5’-monophospate (OMP), and orotidine-5’-monophospate decarboxylase (ODC), which decraboxylates OMP to uridine monophosphate (UMP).

Hereditary orotic aciduria is extremely rare, with approximately 20 reported cases to date. The disorder shows autosomal recessive inheritance and is not confined to any particular ethnic group. The vast majority of affected patients have deficiency of both OPRT and ODC catalytic activities and were formerly classified as having Type I hereditary orotic aciduria (OMIM #258900). However, there is at least one reported individual who was found to have deficiency of ODC catalytic activity with normal to increased expression of OPRT. This individual was categorized as having Type II hereditary orotic aciduria (formerly reported under OMIM #258920). At present, all cases of hereditary orotic aciduria, regardless of type, are reported under OMIM #258900.

Mutations within the UMPS gene (OMIM 613891) are the only known cause of orotic aciduria. The gene is located on chromosome 3q13, consists of 6 exons, and encodes a protein that is 480 amino acids in length (Suchi et al., 1997). While the first 214 amino acids found in the N-terminus contain OPRT, the last 258 amino acids at the C-terminus contain OMP decarboxylase (Suttle et al., 1988). Missense mutations which lead to amino acid substitutions are a common cause of disease; such mutations are known to decrease steady-state levels of the enzyme, impair substrate binding, and reduce catalytic efficiency (Perry et al., 1989; Winkler et al, 1988; Suchi et al., 1997).

Clinical Sensitivity - Sequencing with CNV PGxome

The sensitivity of this test is currently unknown, as comprehensive assessments of sensitivity using direct sequencing methods have not been cited in the published literature for this extremely rare disorder.

The sensitivity of duplication/deletion testing for this extremely rare disorder is currently unknown. However, it should be noted that no gross duplications or deletions in the UMPS gene have been published to date (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the UMPS gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with hereditary orotic aciduria and family members of patients who have known UMPS mutations. In addition, patients with orotic aciduria and megaloblastic anemia who are suspected to have UMP synthase deficiency also are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in UMPS.


Official Gene Symbol OMIM ID
UMPS 613891
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Orotic Aciduria AR 258900


  • Huguley, CM Jr, Bain,  JA, Rivers, SL, Scoggins, RB.et al. 1959. Refractory megaloblastic anemia associated with excretion of orotic acid.  Blood. 14:615-634. PubMed ID: 13651334
  • Human Gene Mutation Database (Bio-base).
  • Nyhan, WL et al. 2012. Orotic aciduria. In: Atlas of Inherited Metabolic Disease (3rd Edition). London:  Hodder Arnold Co. Chapter 69:518-521. 
  • Perry, ME, Jones, M.E. 1989. Orotic aciduria fibroblasts express a labile form of UMP synthase. J. Biol. Chem. 264:15522-15528 PubMed ID: 2475503
  • Suchi, M, Mizuno, H, Kawai, Y, Tsuboi, T, Sumi, S, Okajima, K, Hodgson, ME, Ogawa, H, Wada, Y. 1997. Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Am. J. Hum. Genet. 60:525-539. PubMed ID: 9042911
  • Sumi, S, Suchi, M, Kidouchi, K, Morishita, H, Ohba, S, Wada, Y. et al. 1997. Pyrimidine metabolism in hereditary orotic aciduria. J. Inherit. Metab. Dis. 20: 104-105. PubMed ID: 9061575
  • Suttle, DP, Bugg, BY, Winkler, JK, Kanalas, JJ.. 1988. Molecular cloning and nucleotide sequence for the complete coding region of human UMP synthase. Proc. Natl. Acad. Sci. U. S. A. 85:1754-1758. PubMed ID: 3279416
  • Van Kuilenburg, A.B.P. et al. 2012. Hereditary Orotic Aciduria and Other Disorders of Pyrimidine Metabolism.  In: The Online Metabolic and Molecular Bases of Inherited Disease. Part 11, Chapter 113.
  • Winkler, JK, Suttle, DP. 1988. Analysis of UMP synthase gene and mRNA structure in hereditary orotic aciduria fibroblasts. Am. J. Hum. Genet. 43:86-94. PubMed ID: 2837086


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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