refers to an excessive excretion of orotic acid
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
It can also arise secondary to blockage of the urea cycle, particularly ornithine transcarbamylase deficiency.
In addition to the characteristic excessive orotic acid in the urine, patients typically have megaloblastic anemia which cannot be cured by administration of vitamin B12 or folic acid.
It also can cause inhibition of RNA and DNA synthesis and failure to thrive. This can lead to mental and physical retardation.
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.