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 |
Comments |
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Hereditary orotic aciduria (258900*) |
Uridine monophosphate synthase |
Biochemical profile: Elevated urinary orotate Clinical features: Megaloblastic anemia, recurrent infections, cellular immunodeficiency, developmental disabilities Treatment: Uridine, uridylic and cytidylic acid |
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Dihydropyrimidine dehydrogenase deficiency (274270*) |
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 |
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Dihydropyrimidinuria (222748*) |
Dihydropyrimidinase |
Biochemical profile: Elevated urinary dihydrouracil and dihydrothymine Clinical features: Variable; feeding problems, seizures, lethargy, somnolence, metabolic acidosis Sometimes benign Treatment: Not established |
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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 |
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Pyrimidine 5′ nucleotidase deficiency (266120*) |
5′-Monophosphate hydrolase |
Biochemical profile: No specific profile Clinical features: Hemolytic anemia, basophilic stippling Treatment: Supportive care |
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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 |
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* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man® (OMIM®) database. |
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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.
