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Defects of ornithine cycle enzymes
Last reviewed: 23.04.2024
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Defects of the ornithine cycle enzymes are characterized by hyperammonemia under conditions of catabolism or protein loading.
Primary disorders of the ornithine cycle include a deficiency of carbamoyl phosphate synthetase (CFS), deficiency of arginine succinate synthetase (citrullinemia), deficiency of arginine succinate synthetase (arginine-succinic aciduria) and arginine deficiency (argininemia). There are also reports of a deficiency of N-acetylglutamate synthetase (NACS). The higher the defective enzyme is, the more pronounced hyperammonemia; therefore, the diseases in order of decreasing severity are as follows: deficiency of NSCA, deficiency of CFS, OTC, citrullineemia, arginine-amber acidura and argininemia.
The type of inheritance of all disturbances of the ornithine cycle is autosomal recessive, with the exception of a deficiency in the OTC, which is Hscepted.
[Symptoms of ornithine cycle disruption
Clinical symptoms of the disorder of the ornithine cycle range from mild (eg, hypotrophy, mental retardation, episodic hyperammonemia) to severe (eg, impaired consciousness, coma, death). Manifestations in female patients with OTC deficiency range from a delay in physical and neuropsychic development, psychiatric disorders, and episodic (especially after childbirth) hyperammonemia to a phenotype similar to that of male patients.
Diagnosis of ornithine cycle disruption
The diagnosis is based on the definition of the amino acid profile. For example, an elevated level of ornithine indicates a deficiency of CFS or OTC, while elevation of citrulline to citrullineemia. In order to differentiate the deficiency of CFC from the deficiency of OTC, the level of orotic acid is determined, since the accumulation of carbamoyl phosphate in the absence of OTC leads to the activation of an alternative pathway of its metabolism to orotic acid.
Treatment of ornithine cycle disruption
Treatment of ornithine cycle disorders involves protein restriction in food, but not completely, but only to meet the body's amino acid needs for growth, development and normal protein metabolism. Arginine has become an important part of the treatment. It supplies enough intermediate products of the ornithine cycle to stimulate the introduction of more nitrogen into the intermediate products of the ornithine cycle, each of which is well excreted. Arginine is also a positive regulator of the synthesis of acetylglutamate. Recent studies have suggested that oral administration of citrulline is more effective than arginine in patients with a deficiency of OTC. Additional treatment includes sodium benzoate, phenylbutyrate or phenylacetate, which, by conjugation of glycine (sodium benzoate) and glutamine (phenylbutyrate and phenylacetate), bind and remove nitrogen. Despite the progress in treatment, in many cases the disturbance of the ornithine cycle is still difficult to treat, and many patients eventually need a liver transplant.
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