Argininosuccinate Lyase Deficiency Treatment & Management
- Author: Karl S Roth, MD; Chief Editor: Maria Descartes, MD more...
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. Inclusion of arginine in the regimen helps to offset the inability of deficient tissues to generate free arginine from ASA.
Glycerol phenylbutyrate is a pre-prodrug that undergoes metabolism to form phenylacetate. Results of a phase 3 study comparing ammonia control in adults showed glycerol phenylbutyrate was noninferior to sodium phenylbutyrate. In a separate study involving young children ages 2 months through 5 years, glycerol phenylbutyrate resulted in a more evenly distributed urinary output of PAGN over 24 hours and accounted for fewer symptoms from accumulation of phenylacetate.
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.
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