Medical expert of the article
New publications
Defects in ornithine cycle enzymes
Last reviewed: 07.07.2025
All iLive content is medically reviewed or fact checked to ensure as much factual accuracy as possible.
We have strict sourcing guidelines and only link to reputable media sites, academic research institutions and, whenever possible, medically peer reviewed studies. Note that the numbers in parentheses ([1], [2], etc.) are clickable links to these studies.
If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please select it and press Ctrl + Enter.
Defects in ornithine cycle enzymes are characterized by hyperammonemia under conditions of catabolism or protein loading.
Primary disorders of the urea cycle include carbamoyl phosphate synthetase (CPS) deficiency, ornithine transcarbamylase (OTC) deficiency, arginine succinate synthetase deficiency (citrullinemia), argininosuccinate lyase deficiency (arginine succinic aciduria), and arginase deficiency (argininemia). N-acetylglutamate synthetase (NAGS) deficiency has also been reported. The higher up the defective enzyme, the more severe the hyperammonemia; therefore, the disorders are ranked in decreasing order of severity as follows: NAGS deficiency, CPS deficiency, OTC deficiency, citrullinemia, arginine succinic aciduria, and argininemia.
The inheritance pattern of all urea cycle disorders is autosomal recessive, with the exception of OTC deficiency, which is X-linked.
[ Symptoms of ornithine cycle disorder
Clinical manifestations of urea cycle disorders range from mild (eg, malnutrition, mental retardation, episodic hyperammonemia) to severe (eg, impaired consciousness, coma, death). Manifestations in female patients with urea cycle deficiency range from delayed physical and neurodevelopmental development, psychiatric disturbances, and episodic (especially postpartum) hyperammonemia to a phenotype similar to that in male patients.
Diagnosis of ornithine cycle disorder
The diagnosis is based on the determination of the amino acid profile. For example, elevated ornithine indicates a deficiency of the CPS or OTC, while elevated citrulline indicates citrullinemia. In order to differentiate the deficiency of the CPS from the OTC deficiency, the level of orotic acid is determined, since the accumulation of carbamoyl phosphate in OTC deficiency leads to the activation of an alternative pathway for its metabolism to orotic acid.
Treatment of ornithine cycle disorder
Treatment of urea cycle disorders involves restricting dietary protein, but not completely, but only enough to provide the amino acid requirements for growth, development, and normal protein turnover. Arginine has become a critical part of treatment. It supplies enough urea cycle intermediates to stimulate the incorporation of more nitrogen moieties into urea cycle intermediates, all of which are readily excreted. Arginine is also a positive regulator of acetylglutamate synthesis. Recent studies have suggested that oral citrulline is more effective than arginine in patients with urea cycle deficiency. Additional treatments include sodium benzoate, phenylbutyrate, or phenylacetate, which, by conjugating glycine (sodium benzoate) and glutamine (phenylbutyrate and phenylacetate), allow nitrogen binding and excretion. Despite advances in treatment, many urea cycle disorders remain difficult to treat, and many patients eventually require liver transplantation.
Использованная литература