Urea cycle hereditary metabolic disorders

Hereditary Metabolic Disorders of the Urea Cycle B. Levin... 

The determination of plasma ammonia is of great importance both for the diagnosis and for the treatment of hereditary metabolic disorders of the urea cycle. The level is always raised in these conditions since the other mechanisms for regulating blood ammonia mentioned above are not able by themselves to keep the ammonia level within normal limits. 

Bachmann C, Colombo JP. Acid-base status and plasma glutamine in patients with hereditary urea cycle disorders. In Soeters PB, Wilson )HP, Meijer AJ, eds. Advances in ammonia metabolism and hepatic encephalopathy, 1st ed. Amsterdam Elsevier, 1988 72-8. 

Deficiency of folate or vitamin Bn can cause hematological changes similar to hereditary orotic aciduria. Folate is directly involved in thymidylic acid synthesis and indirectly involved in vitamin Bn synthesis. Orotic aciduria without the characteristic hematological abnormalities occurs in disorders of the urea cycle that lead to accumulation of carbamoyl phosphate in mitochondria (e.g., ornithine transcarbamoylase deficiency see Chapter 17). The carbamoyl phosphate exits from the mitochondria and augments cytosolic pyrimidine biosynthesis. Treatment with allopurinol or 6-azauridine also produces orotic aciduria as a result of inhibition of orotidine-5 phosphate decarboxylase by their metabolic products. 

Intoxication disorders include urea cycle disorders, organic acidurias, aminoacidopathies, fatty acid oxidation disorders, and carbohydrate disorders such as galactosemia or hereditary fructose intolerance. In these disorders, a partial or complete lack of enzymatic activity causes the accumulation of substances proximal to the metabolic block in tissues and body fluids, where they act as toxins (Fig. 5.1). Treatment is based on limiting the substances that are the source of the toxic metabolites and introducing alternatives (e.g., drugs, procedures) that speed the elimination of those toxic metabolites. 

---