Orotic aciduria

Orotic aciduria refers to an excessive excretion of orotic acid in urine.

Signs and symptoms
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.

Cause and Genetics
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 in ornithine transcarbamylase deficiency (or OTC deficiency). You can distinguish this increase in orotic acid secondary to OTC deficiency from hereditary orotic aciduria (seen above) by looking at blood ammonia levels and the BUN. In OTC deficiency, because the urea cycle backs up, you will see hyperammonemia and a decreased BUN.

Treatment
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.