Disorders of the Urea Cycle and Related Enzymes

  • James V. Leonard


Six inherited disorders of the urea cycle are well described (Fig. 20.1). These are the deficiencies of carbamoyl phosphate synthetase (CPS), ornithine transcarbamoylase (OTC), argininosuccinate synthetase, argininosuccinate lyase, arginase, and N-acetylglutamate synthetase (NAGS). Deficiencies of glutamine synthetase and of citrin have also been described. All these defects are characterised by hyperammonaemia and disordered amino acid metabolism. The presentation is highly variable: those presenting in the newborn period usually have an overwhelming illness that rapidly progresses from poor feeding, vomiting, lethargy or irritability and tachypnoea to fits, coma and respiratory failure. In infancy, the symptoms are less severe and more variable. Poor developmental progress, behavioural problems, hepatomegaly and gastrointestinal symptoms are common. Children and adults frequently have a chronic neurological illness that is characterised by variable behavioural problems, confusion, irritability and episodic vomiting. However, during any metabolic stress the patients may become acutely unwell. Arginase deficiency has more specific symptoms, such as spastic diplegia, dystonia, ataxia and fits. All these disorders have autosomal- recessive inheritance except ornithine transcarbamoylase deficiency, which is X-linked.


Urea Cycle Sodium Benzoate Orotic Acid Carbamoyl Phosphate Carbamoyl Phosphate Synthe 
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Copyright information

© Springer Medizin Verlag Heidelberg 2006

Authors and Affiliations

  • James V. Leonard
    • 1
  1. 1.Biochemistry, Endocrinology and Metabolic UnitInstitute of Child Health, Great Ormond Street Hospital for ChildrenLondonUK

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