eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases
Citrullinemia: Treatment & Medication
Updated: Mar 26, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- As in all hyperammonemic states, immediately restrict dietary protein in patients with citrullinemia. Emphasize other nonprotein caloric sources to compensate.
- Intravenous sodium benzoate, sodium phenylacetate, and arginine are important therapeutic avenues for reduction of blood ammonia levels. Intravenous benzoate and phenylacetate are investigational new drugs. In severe cases, hemodialysis may be indicated to rapidly reduce the blood ammonia level.
- Long-term management requires close dietary monitoring and oral administration of sodium phenylbutyrate and arginine.
- In every case, a biochemical geneticist should administer definitive short- and long-term treatment with sufficient laboratory backup to obtain rapid ammonia and amino acid levels.
Consultations
- Geneticist
- Metabolic disease specialist
- Dietitian
Diet
- As in all hyperammonemic states, immediately restrict dietary protein in patients with citrullinemia.
- Emphasize other nonprotein caloric sources to compensate.
Medication
Metabolic agents
The use of benzoate and phenylacetate is based on the need to provide alternate routes for waste nitrogen disposal. Benzoate is transaminated to form hippuric acid, which is rapidly cleared by the kidney. Phenylacetate is converted to phenylacetyl CoA and then conjugated with glutamine to form phenylacetylglutamine. Each of these pathways results in disposition of 1 and 2 molecules of ammonia, respectively. Phenylbutyrate is more acceptable as a form of oral therapy because of a diminished odor but is not available for intravenous use.
Sodium benzoate and sodium phenylacetate (Ucephan, Ammonul)
Combines with glycine to form hippurate, which is excreted in urine. One mol of benzoate removes 1 mol of nitrogen. The oral product (Ucephan) and IV product (Ammonul) contain a combination of sodium benzoate (10 g) and sodium phenylacetate (10 g per 100 mL; 100 mg of each/mL).
Adult
Pediatric
Ammonul 10% injection (100 mg/mL)
Loading dose: 250 mg (2.5 mL)/kg IV infused over 90 min via central line
Maintenance dose: 250 mg (2.5 mL)/kg IV infused over 24 h via central line
Dilute IV dose in 30 mL/kg of dextrose 10%
Ucephan
Oral maintenance dose: 375 mg/kg/d PO divided tid/qid in conjunction with a low-protein diet
Penicillin may decrease effects; probenecid may inhibit renal excretion of products; valproate may antagonize efficacy
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution when administering to patients with neonatal hyperbilirubinemia (competes for bilirubin-binding sites on albumin); because of sodium content, exercise caution when administering to patients with CHF, severe renal dysfunction, and sodium retention with edema; common adverse effects include nausea, vomiting, tinnitus, and visual disturbances; IV must be diluted with dextrose 10% and administered via central line; phenylacetate may cause neurotoxicity; typically administered with antiemetic to prevent common occurrence of nausea and vomiting; caution in severe congestive heart failure or severe renal insufficiency because it contains large amount of sodium (30.5 mg/mL in undiluted IV product)
Sodium phenylbutyrate (Buphenyl)
Prodrug rapidly converted orally to phenylacetylglutamine, which serves as substitute for urea and is excreted in the urine, carrying 2 mol of nitrogen per mol of phenylacetylglutamine, assisting in clearance of nitrogenous waste.
Adult
Pediatric
0.5 g/kg/d PO divided tid pc
Valproate and haloperidol may increase ammonia levels
Documented hypersensitivity; severe hypertension; heart failure; renal dysfunction; acute hyperammonemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Because of sodium content, avoid in patients with CHF, severe renal dysfunction, and sodium retention with edema
Arginine (R-Gene 10)
Provides 1 mol of urea plus 1 mol ornithine per mol of arginine when cleaved by arginase. Pituitary stimulant for the release of human growth hormone (HGH). Often induces pronounced HGH levels in patients with intact pituitary function. Available as 10% injection (100 mg/mL).
Adult
Pediatric
Hyperammonemic crisis:
Loading dose: 600 mg/kg IV (not to exceed 1 g/kg/h)
IV maintenance dose: 600 mg/kg/d IV as a continuous infusion
Dilute IV in 30 mL/kg of dextrose 10%
Maintenance treatment in a stable child: 400-700 mg (as free base)/kg/d PO
Coadministration with amphotericin, triamterene, amiloride, or spironolactone may increase risk of hyperkalemia
Documented hypersensitivity; renal or hepatic failure
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Renal impairment; diagnostic aid not intended for therapeutic use: administer only in a large medical facility with close laboratory monitoring available; may cause nausea, vomiting, headache, hyperkalemia, hyperglycemia, or venous irritation during IV administration
More on Citrullinemia |
| Overview: Citrullinemia |
| Differential Diagnoses & Workup: Citrullinemia |
 Treatment & Medication: Citrullinemia |
| Follow-up: Citrullinemia |
| Multimedia: Citrullinemia |
| References |
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References
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Further Reading
Keywords
citrullinemia, citrulline, argininosuccinic acid synthase deficiency, citrullinuria, aminoaciduria, ornithine transcarbamylase reaction, argininosuccinic acid, ASA, ASA synthase, carbamyl phosphate synthetase reaction, CPS reaction, waste nitrogen disposal, hyperammonemia, mental retardation, urea cycle defect, neonatal intrahepatic cholestasis, NICCD, hepatomegaly, treatment, diagnosis
