Not Found
Locations

Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.

* This is the Professional Version. *

Pyrimidine Metabolism Disorders

By Lee M. Sanders, MD, MPH, Stanford University

Click here for
Patient Education

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 Table ).

Pyrimidine Metabolism Disorders

Disease (OMIM Number)

Defective Proteins or Enzymes

Defective Gene or Genes (Chromosomal Location)

Comments

Biochemical profile: Elevated urinary orotate

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

Treatment: Uridine, uridylic and cytidylic acid

Type I (258900)

UMP synthase (orotidine-5-pyrophosphorylase and decarboxylase)

UMPS (3q13)*

Type II (258920)

Orotidine-5-decarboxylase

Dihydropyrimidine dehydrogenase deficiency (274270)

  • Inborn error form

  • Pharmacogenetic form

Dihydropyrimidine dehydrogenase

DPYD (1p22)*

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, GI and skin symptoms, death

Treatment: No specific treatment except for withdrawal of offending drug

Dihydropyrimidinuria (222748)

Dihydropyrimidinase

DPYS (8q22)*

Biochemical profile: Elevated urinary dihydrouracil and dihydrothymine

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

Sometimes benign

Treatment: Not established

β-Ureido propionase deficiency (210100)

β-Ureido propionase (β-alanine synthase)

UPB1 (22q11.2)

Biochemical profile: Elevated urinary ureidopropionate and ureidobutyrate

Clinical features:Microcephaly, developmental delay, dystonia, scoliosis

Treatment: Not established

Pyrimidine 5nucleotidase deficiency (266120)

5-Monophosphate hydrolase

NT5C3 (7p15-p14)*

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

AICDA (12p13)*

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

Clinical features: Recurrent bacterial infections, defective Ig class switching

Treatment: Control of infections

*Gene has been identified, and molecular basis has been elucidated.

OMIM = online mendelian inheritance in man (see the 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 enzyme assay in a variety of tissues. (Also see testing for suspected inherited disorders of metabolism.)

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

Resources In This Article

* This is the Professional Version. *