Orotic aciduria hereditary




A rare metabolic disorder where an inherited enzyme deficiency (lack of orotidylic pyrophosphorylase and orotidylic decarboxylase or a lack of orotidylic decarboxylase only) impairs the body's ability to break down orotic acid, leading to excessive excretion of orotic acid in urine. It causes a characteristic form of anemia and may be associated with mental and physical retardation.


Signs and symptoms:

  • Excessive orotic acid in the urine
  • Megaloblastic anemia
  • Delays in physical and intellectual development


Its hereditary form, an autosomal recessive disorder, can be caused by a deficiency in the enzyme UMPS, a bifunctional protein that includes the enzyme activities of orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase. Orotic aciduria has an autosomal recessive of inheritance. It can also arise secondary to blockage of the urea cycle, particularly ornithine transcarbamylase deficiency.


Orotic aciduria type I is diagnosed by a urine test to measure the amount of orotic acid; the urine of affected individuals has very high amounts of orotic acid.


Administration of cytidine monophosphate and uridine monophosphate reduces urinary orotic acid and the anemia. Administration of uridine, which is converted to UMP, will bypass the metabolic block and provide the body with a source of pyrimidine.

Uridine triacetate -  FDA-approved indication: Treatment of hereditary orotic aciduria.