The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia. Ammonia is especially damaging to the nervous system, so argininosuccinic aciduria causes neurological problems as well as eventual damage to the liver.This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder. Diagnosis
Diagnosis is based mainly on clinical findings and laboratory test results. Plasma concentrations of ammonia (>150 μmol/L) and citrulline (200-300 μmol/L) are elevated. Elevated levels of argininosuccinic acid (5-110 μmol/L) in the plasma or urine are diagnostic. Molecular genetic testing confirms diagnosis. Newborn screening for ASA is available in the U.S. and parts of Australia, and is considered in several European countries

Treatment
During an acute hyperammonemic episode, oral proteins must be avoided and 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, but if unsuccessful, hemodialysis is recommended. Long-term management involves dietary protein restriction as well as arginine supplementation. In those with frequent episodes of metabolic decompensation or with hyperammonemia even when following a protein-restricted diet, daily oral nitrogen scavenging therapy may be successful. Orthotopic liver transplantation offers long-term relief of hyperammonemia but does not seem to sufficiently correct neurological complications.
Arterial hypertension can be treated by restoring nitric oxide deficiency

Prognosis
Due to the rarity of the disease, it is hard to estimate mortality rates or life expectancy. One 2003 study which followed 88 cases receiving two different kinds of treatment found that very few persons lived beyond age 20 and none beyond age 30. Incidence
Argininosuccinic aciduria occurs in approximately 1 in 70,000 live births. Many patients can now be detected on the newborn screen if their blood citrulline is elevated. References
Literature
Kleijer WJ, Garritsen VH, Linnebank M, Mooyer P, Huijmans JG, Mustonen A, Simola KO, Arslan-Kirchner M, Battini R, Briones P, Cardo E, Mandel H, Tschiedel E, Wanders RJ, Koch HG (2002). "Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families". J Inherit Metab Dis. 25 (5): 399–410. doi:10.1023/A:1020108002877. PMID 12408190. S2CID 11129281. Lee B, Goss J (2001). "Long-term correction of urea cycle disorders". J Pediatr. 138 (1 Suppl): S62–71. doi:10.1067/mpd.2001.111838. PMID 11148551. Reid Sutton V, Pan Y, Davis EC, Craigen WJ (2003). "A mouse model of argininosuccinic aciduria: biochemical characterization". Mol Genet Metab. 78 (1): 11–6. doi:10.1016/S1096-7192(02)00206-8. PMID 12559843. Scaglia F, Brunetti-Pierri N, Kleppe S, Marini J, Carter S, Garlick P, Jahoor F, OBrien W, Lee B (2004). "Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism". J Nutr. 134 (10 Suppl): 2775S–2782S, discussion 2796S–2797S. doi:10.1093/jn/134.10.2775S. PMID 15465784. Full text
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