eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases
Argininosuccinate Lyase Deficiency: Treatment & Medication
Updated: Mar 24, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Immediate temporary withdrawal of protein is indicated in all patients with newly discovered hyperammonemia. Increase nonprotein caloric sources to avoid catabolism of muscle protein for energy.
- Intravenous benzoate, arginine, and phenylacetate administration may be indicated as initial therapy for hyperammonemia, but such combined therapy is appropriate only prior to specific diagnosis. Hemodialysis, if available, reduces the blood ammonia levels more efficiently and quickly.
- Long-term therapy should involve a low-protein diet and arginine supplementation. This diet helps produce equivalent quantities of ornithine for enhancement of urea cycle activity up to the point of argininosuccinate (ASA) lyase and, thus, enhances waste nitrogen incorporation.
Surgical Care
- For several years, liver transplantation has been the accepted form of surgical treatment for urea cycle disorders. However, many patients have delayed development, physical debilitation, or both, disqualifying them from the procedure or greatly increasing the associated risks.
- Donor cell engraftment has been reported to be an effective technique of reducing the acuity of the disease in patients with neonatal-onset ASA lyase deficiency. This modality may offer a safer approach to surgical treatment of urea cycle disorders in general and may reduce the need for patients to qualify for a place on a transplantation roster.
Consultations
- Medical geneticist
- Metabolic disease specialist
- Pediatric critical care specialist
- Dietitian
Diet
- See Medical Care.
Medication
Because the enzyme defect interrupts the urea cycle, alternative means of waste nitrogen disposal are required. Some medications assist in excreting nitrogen and serve as an alternative to urea to reduce waste nitrogen levels. Administer only in a large medical facility with close laboratory monitoring.
Nitrogen reducers
These are used in management of severe, uncompensated metabolic alkalosis.
Arginine HCl (R-Gene)
Enhances production of ornithine, which facilitates incorporation of waste nitrogen into the formation of citrulline and ASA.
Adult
Pediatric
Hyperammonemic crisis: 0.66 g/kg IV over 24 h, diluted in 25-35 mL 10% dextrose
Maintenance treatment of a stable child: 0.4-0.7 g/kg/d PO administered as free base
Increased toxicity of estrogen-progesterone combinations due to growth hormone response and glucagon and insulin effects; spironolactone may cause potentially fatal 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
May cause mild-to-moderate metabolic acidosis; may cause nausea, vomiting, headache, hyperkalemia, hyperglycemia, or venous irritation during IV administration
Sodium phenylacetate and sodium benzoate (Ammonul)
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 mol is identical to that of urea (2 mol of nitrogen). Ammonul must be administered with arginine for carbamyl phophate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), or ASA 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.
Adult
Ammonul
Loading: 55 mL (5.5 g)/m2 IV over 90-120 min via central line
Maintenance: 55 mL (5.5 g)/m2/d IV over 24 h via central line
Must dilute IV dose in at least 25 mL/kg of dextrose 10% before administration
Pediatric
Ammonul
<20 kg:
Loading: 2.5 mL (250 mg)/kg IV over 90-120 min via central line
Maintenance: 2.5 mL (250 mg)/kg/d IV over 24 h via central line
Must dilute IV dose in at least 25 mL/kg of dextrose 10% before administration
>20 kg: Administer as in adults
Penicillin may decrease effects of sodium benzoate and sodium phenylacetate; probenecid may inhibit renal excretion of products of sodium benzoate and sodium phenylacetate; valproate may antagonize efficacy of sodium benzoate and sodium phenylacetate; corticosteroids may increase body protein metabolism, thereby increasing plasma ammonia levels; do not use concomitantly with PO sodium phenylbutyrate (Buphenyl) because of additive effects
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 congestive heart failure, severe renal dysfunction, and sodium retention with edema; common side effects include nausea, vomiting, tinnitus, and visual disturbance; 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 a large amount of sodium (30.5 mg/mL in undiluted IV product)
More on Argininosuccinate Lyase Deficiency |
| Overview: Argininosuccinate Lyase Deficiency |
| Differential Diagnoses & Workup: Argininosuccinate Lyase Deficiency |
 Treatment & Medication: Argininosuccinate Lyase Deficiency |
| Follow-up: Argininosuccinate Lyase Deficiency |
| Multimedia: Argininosuccinate Lyase Deficiency |
| References |
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References
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Stadler S, Gempel K, Bieger I, et al. Detection of neonatal argininosuccinate lyase deficiency by serum tandem mass spectrometry. J Inherit Metab Dis. Jun 2001;24(3):370-8. [Medline].
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Stephenne X, Najimi M, Sibille C, Nassogne MC, Smets F, Sokal EM. Sustained engraftment and tissue enzyme activity after liver cell transplantation for argininosuccinate lyase deficiency. Gastroenterology. Apr 2006;130(4):1317-23. [Medline].
Trevisson E, Salviati L, Baldoin MC, et al. Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene. Hum Mutat. Feb 26 2007;28(7):694-702. [Medline].
Widhalm K, Koch S, Scheibenreiter S, et al. Long-term follow-up of 12 patients with the late-onset variant of argininosuccinic acid lyase deficiency: no impairment of intellectual and psychomotor development during therapy. Pediatrics. Jun 1992;89(6 Pt 2):1182-4. [Medline].
Further Reading
Keywords
argininosuccinase, ASA, argininosuccinase lyase deficiency, ASA lyase deficiency, argininosuccinic aciduria, argininosuccinase deficiency, hyperammonemia, hepatic urea cycle, -acetylglutamate, carbamyl phosphate synthetase, CPS, trichorrhexis nodosa, friable hair, choreoathetotic movement disorder, ASL deficiency, diagnosis, treatment, mental retardation, respiratory failure
