Signs and symptoms

In addition to the characteristic excessive orotic acid in the urine, patients typically have megaloblastic anemia

Megaloblastic anemia

Megaloblastic anemia is an anemia that results from inhibition of DNA synthesis in red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis stage...

 which cannot be cured by administration of vitamin B12

Vitamin B12

Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...

 or folic acid

Folic acid

Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...

.

It also can cause inhibition of RNA

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 and DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 synthesis and failure to thrive. This can lead to mental and physical retardation.

Cause and Genetics

Its hereditary form, an autosomal recessive

Recessive

In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...

 disorder, can be caused by a deficiency in the enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 UMPS, a bifunctional protein that includes the enzyme activities of orotate phosphoribosyltransferase

Orotate phosphoribosyltransferase

Orotate phosphoribosyltransferase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the formation of orotidine 5'-monophosphate from orotate and phosphoribosyl pyrophosphate...

 and orotidine 5'-phosphate decarboxylase

Orotidine 5'-phosphate decarboxylase

Orotidine 5’-phosphate decarboxylase or orotidylate decarboxylase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the decarboxylation of orotidine monophosphate to form uridine monophosphate...

.

It can also arise secondary to blockage of the urea cycle

Urea cycle

The urea cycle is a cycle of biochemical reactions occurring in many animals that produces urea from ammonia . This cycle was the first metabolic cycle discovered , five years before the discovery of the TCA cycle...

, particularly in ornithine transcarbamylase deficiency

Ornithine transcarbamylase deficiency

Ornithine transcarbamylase deficiency , the most common of the urea cycle disorders, is a rare metabolic disorder, occurring in one out of every 80,000 births...

 (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

Cytidine monophosphate

Cytidine monophosphate, also known as 5'-cytidylic acid or simply cytidylate, and abbreviated CMP, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside cytidine...

 and uridine monophosphate

Uridine monophosphate

Uridine monophosphate, also known as 5'-uridylic acid and abbreviated UMP, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside uridine...

 reduces urinary orotic acid and the anemia.

Administration of uridine

Uridine

Uridine is a molecule that is formed when uracil is attached to a ribose ring via a β-N1-glycosidic bond.If uracil is attached to a deoxyribose ring, it is known as a deoxyuridine....

, which is converted to UMP, will bypass the metabolic block and provide the body with a source of pyrimidine

Pyrimidine

Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...

.