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Management of urea cycle disorders

INTRODUCTION

The urea cycle is the metabolic pathway that transforms nitrogen to urea for excretion from the body (algorithm 1). Deficiency of an enzyme in the pathway causes a urea cycle disorder (UCD). The urea cycle disorders are:

  • Carbamyl phosphate synthetase I (CPSI) deficiency (OMIM #237300)
  • Ornithine transcarbamylase (OTC) deficiency (OMIM #311250)
  • Argininosuccinate synthetase (ASS) deficiency (also known as classic citrullinemia or type I citrullinemia, CTLN1, OMIM #215700)
  • Argininosuccinate lyase deficiency (ASL, also known as argininosuccinic aciduria, OMIM #207900)
  • N-acetyl glutamate synthetase (NAGS) deficiency (OMIM#237310)
  • Arginase deficiency (OMIM #207800)

UCDs, except for arginase deficiency, result in hyperammonemia and life-threatening illnesses. Survivors of the metabolic decompensation frequently have severe neurologic injury. Prompt recognition and treatment are needed to improve outcome.

The management of urea cycle disorders will be discussed here. The clinical features and diagnosis of urea cycle disorders is discussed separately. (See "Clinical features and diagnosis of urea cycle disorders".)

INITIAL MANAGEMENT

Neurologic abnormalities and impaired cognitive function have significant correlation with the duration of hyperammonemia and encephalopathy [1,2]. Thus, treatment should be initiated as soon as a UCD is suspected and should proceed concurrently with the diagnostic evaluation.
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