Argininosuccinate Lyase deficiency is an autosomal recessive disorder. Affected individuals have mutations in the gene coding for the enzyme argininosuccinate lyase (ASL), which is involved in the urea cycle.
Treatment of ASL deficiency involves two scenarios.
- Rapid control of hyperammonemia during metabolic decompensations. The management of hyperammonemia includes discontinuing the oral protein intake, caloric supplementation with intravenous glucose and lipids with the initiation of intravenous nitrogen scavenging drugs.
- Chronic management of ASL deficiency: This mode includes dietary restriction of protein and arginine supplementation. Patients who have had frequent metabolic decompensations or elevated ammonia are candidates for additional oral nitrogen scavenging therapy with either sodium benzoate or sodium phenylbutyrate
- Dietary therapy, along with arginine supplements, has shown to reverse abnormalities of hair and improve cognitive outcomes, including reversal of abnormalities on EEG.
- Orthotopic Liver Transplantation (OLT) offers long terms cure for the disease. However, OLT is recommended only for patients with recurrence of hyperammonaemia and metabolic decompensations, which are resistance to conventional treatment. OLT does not correct the abnormalities of deficiency of tissue-specific arginine and elevation of argininosuccinate.
- Note: the ideal dosing of arginine and its utility is still unclear, as magnetic resonance spectroscopy of brains in the patients on arginine supplementation has shown elevation of guanidinoacetate.
Developmental delay,Mental retardation,Progressive liver damage,Skin lesions,Brittle hair
Intravenous (I.V.) lipids, glucose and insulin (if needed) should be given to promote anabolism,I.V. nitrogen scavenging therapy (with sodium benzoate and/or sodium phenylacetate) should normalize ammonia levels,Hemodialysis
Abnormally diminished muscle tone (hypotonia),Poor feeding,Vomiting,Lethargy,Seizures