Genetics of Hyperammonemia-Hyperornithinemia-Homocitrullinuria (HHH) Syndrome Medication

Updated: Jan 07, 2019
  • Author: Richard E Frye, MD, PhD; Chief Editor: Maria Descartes, MD  more...
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Medication

Medication Summary

Sodium benzoate and sodium phenylacetate may reduce ammonia levels by providing an alternative pathway.

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Urea Cycle Disorder Treatment Agents

Class Summary

These agents assist in excreting nitrogen and serve as an alternative to urea in reducing waste nitrogen levels. Administer only in a large medical facility with close laboratory monitoring available.

Sodium phenylacetate and sodium benzoate (Ammonul, Ucephan)

Benzoate combines with glycine to form hippurate, which is excreted in urine. One mol of benzoate removes 1 mol of nitrogen. Phenylacetate conjugates (via acetylation) glutamine in the liver and kidneys to form phenylacetylglutamine, which is excreted by the kidneys. The nitrogen content of phenylacetylglutamine per mole is identical to that of urea (2 mol of nitrogen). Ammonul must be administered with arginine for carbamyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, or argininosuccinate lyase deficiencies. Indicated as adjunctive treatment of acute hyperammonemia associated with encephalopathy caused by urea-cycle enzyme deficiencies. Serves as an alternative to urea to reduce waste nitrogen levels.

Glycerol phenylbutyrate (Ravicti)

Glycerol phenylbutyrate is a nitrogen-binding agent for chronic management of adult and pediatric patients (including newborns) with urea cycle disorders who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. It is a pre-prodrug that is metabolized by ester hydrolysis and pancreatic lipases to phenylbutyrate and then by beta oxidation to phenylacetate. Glutamine is conjugated with phenylacetate to form phenylacetylglutamine, a nitrogen waste product that is excreted in the urine. It is not indicated for treatment of hyperammonemia.

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