Orotic Acid

Test ID:

703886

CPT code:

83921; 82570

Clinical Use:

Elevated levels of orotic acid help lead to positive diagnoses of specific urea cycle disorders, including ornithine transcarbamylase deficiency (OTC), citrullinemia, and arginosuccinic aciduria. Rare hereditary disorders may also be diagnosed via elevation of orotic acid, namely orotic aciduria and uridine monophosphate synthase deficiency, which may be physiologically characterized by megaloblastic anemia and crystalluria. Normal levels of orotic acid assist in the accurate differential diagnoses of patients with elevated plasma ammonia and low plasma citrulline and arginine levels caused by liver infections, carbamoylphosphate synthetase I deficiency (CPSI), or N-acetyl glutamate synthetase deficiency (NAGS).

Test Information:

Orotic acid is an intermediary in the metabolism of the nucleotide pyrimidine, immediately following the conversion of carbamoyl phosphate to dihydroorotate in the human mitochondria. Orotic acid is then converted into orotate monophosphate by the activated form of ribose 5-phosphate, 5-phosphoribosyl-1-pyrophosphate, which is delivered in to the urea cycle. The urea cycle is of vital importance to the functions of the body, as it clears unused ammonia and its precursor metabolites through urinary excretions. Ammonia buildup (hyperammonemia) may rapidly develop, manifesting initially as lethargy and vomiting, eventually leading to cerebral edema, coma, and death. Other symptoms urea cycle disorders present include hyper- or hypoventilation, anorexia, hypothermia caused by a lack of thermoregulation, seizures, sleep disorders, delusions (in adult-onset hyperammonemia), and abnormal posturing of the body caused by swelling of the brain and pressure on the brain stem. Urea cycle disorders normally become apparent in early childhood, often a few days after birth, though late-onset variants of these disorders exist. Likewise, female carriers of the X-linked disorder ornithine transcarbamylase (OTC) deficiency may be symptomatic with a variable age of onset. Symptoms in late-onset forms are often triggered by excess stress and/or illness. Many children leave hospital care before defects of the urea cycle become apparent, emphasizing the need for diagnostic tools that provide clinically-relevant information before physical symptoms can present and cause irreversible damage