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.
In this video I have explained orotic aciduria refers to an excessive excretion of orotic acid in urine. It causes a characteristic form of anemia and may be associated with mental and physical retardation.
Orotic acid is an intermediate product in pyrimidine synthesis pathway, a subsequent product of which plays a role in conversion between dihydrofolate and tetrahydrofolate. Orotic aciduria is associated with megaloblastic anemia due to decreased pyrimidine synthesis, which leads to decreased nucleotide-lipid cofactors needed for erythrocyte membrane synthesis in the bone marrow.
In addition to the characteristic excessive orotic acid in the urine, patients typically have megaloblastic anemia (UMP synthase deficiency) 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.
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 (blood urea nitrogen). In OTC deficiency, because the urea cycle backs up, you will see hyperammonemia and a decreased BUN.
Administration of uridine, which is converted to UMP, will bypass the metabolic block and provide the body with a source of pyrimidine. Uridine triacetate is a drug approved by FDA to be used in the treatment of hereditary orotic aciduria.