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Pyrimidine Metabolism Disorders


Matt Demczko

, MD, Sidney Kimmel Medical College of Thomas Jefferson University

Last full review/revision Apr 2020| Content last modified Apr 2020
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Pyrimidines may be synthesized de novo or recycled by a salvage pathway from normal catabolism. The catabolism of pyrimidines produces citric acid cycle intermediates. There are several disorders of pyrimidine metabolism (see the table).


Pyrimidine Metabolism Disorders

Disease (OMIM Number)

Defective Proteins or Enzymes


Uridine monophosphate synthase

Biochemical profile: Elevated urinary orotate

Clinical features: Megaloblastic anemia, recurrent infections, cellular immunodeficiency, developmental disabilities

Treatment: Uridine, uridylic and cytidylic acid

Dihydropyrimidine dehydrogenase deficiency (274270*)

  • Inborn error form

  • Pharmacogenetic form

Dihydropyrimidine dehydrogenase

Biochemical profile: Elevated urinary uracil, thymine, and 5-hydroxymethyluracil

Clinical features: In inborn error form, growth and developmental delay, seizures, spasticity, microcephaly

In pharmacogenetic form, adverse reactions to 5-flurouracil, including myelosuppression, neurotoxicity, gastrointestinal and skin symptoms, death

Treatment: No specific treatment except for withdrawal of offending drug

Dihydropyrimidinuria (222748*)


Biochemical profile: Elevated urinary dihydrouracil and dihydrothymine

Clinical features: Variable; feeding problems, seizures, lethargy, somnolence, metabolic acidosis

Sometimes benign

Treatment: Not established

Beta-ureido propionase deficiency (210100*)

Beta-ureido propionase (beta-alanine synthase)

Biochemical profile: Elevated urinary ureidopropionate and ureidobutyrate

Clinical features: Microcephaly, developmental delay, dystonia, scoliosis

Treatment: Not established

Pyrimidine 5 nucleotidase deficiency (266120*)

5-Monophosphate hydrolase

Biochemical profile: No specific profile

Clinical features: Hemolytic anemia, basophilic stippling

Treatment: Supportive care

Activation-induced cytidine deaminase deficiency (hyper IgM syndrome type II; 605257*)

Activation-induced cytidine deaminase

Biochemical profile: High IgM, low to absent IgG and IgA

Clinical features: Recurrent bacterial infections, defective Ig class switching

Treatment: Control of infections

* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man® (OMIM®) database.

Uridine monophosphate synthase deficiency (hereditary orotic aciduria)

Uridine monophosphate is the enzyme that catalyzes orotate phosphoribosyltransferase and orotidine-5-monophosphate decarboxylase reactions. With deficiency, orotic acid accumulates, causing clinical manifestations of megaloblastic anemia, orotic crystalluria and nephropathy, cardiac malformations, strabismus, and recurrent infections.

Diagnosis of uridine monophosphate synthase deficiency is by DNA analysis and/or enzyme assay in a variety of tissues. (See also testing for suspected inherited disorders of metabolism.)

Treatment of uridine monophosphate synthase deficiency is with oral uridine supplementation.

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