Description, Causes and Risk Factors:

A disorder of urea cycle due to a deficiency of argininosuccinate lyase (AL); characterized by physical and mental retardation, epilepsy, ataxia, liver disease, friable, tufted hair, and excessive urinary excretion of argininosuccinic acid (ASA). Autosomal recessive inheritance, caused by mutation in argininosuccinate lyase gene on chromosome 7q.


Argininosuccinate lyase (AL) has several roles in intermediary metabolism. It is an essential component of the urea cycle, providing a pathway for the disposal of excess nitrogen in mammals. AL links the urea cycle to the tricarboxylic acid (TCA) cycle by generating fumarate. Finally, AL is required for the endogenous production of arginine. In this latter role it may function outside ureagenic organs to provide arginine as a substrate for nitric oxide synthases (NOS). Increasing evidence suggests that argininosuccinate synthetase (ASS) and AL are more globally expressed, and the coordinate regulation of ASS and AL gene expression with that of the inducible form of NOS (i-NOS) provides evidence that this may facilitate the regulation of NOS activity. De?ciency of AL leads to the human urea cycle disorder argininosuccinicaciduria.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

If both members of a couple are carriers, the risk for an affected child is 25% in each pregnancy; therefore, it is especially important that the reproductive partner of a carrier be offered testing.

Argininosuccinicaciduria can occur in individuals of all races and ethnicities. It is estimated to affect 1 in 70,000 live births, with a calculated carrier frequency of 1 in 132.


Symptoms of argininosuccinicaciduria include:


  • Loss of appetite.

  • Erratic breathing.

  • Poorly controlled body temperature.

  • Hepatomegaly.

  • Hypotonia.

  • Apnea.

  • Seizures.

  • Coma.


Diagnosis is made by the existence of hyperammonemia and by chromatography of plasmatic and urinary organic acids that shows accumulation of argininosuccinic acid (ASA).Prenatal diagnosis is possible with enzyme assay of CVS or amniocytes.

No routine laboratory data assist diagnosis of argininosuccinicaciduria.Blood urea nitrogen (BUN) testing is subject to numerous factors aside from the rate of production via the urea cycle. Among the most obvious is the state of hydration, which frequently causes an artifactual increase to a normal concentration in a very sick infant.

A very low BUN level is suggestive but must never be relied on as a diagnostic indicator.

As with all other urea cycle disorders, clinical suspicion is essential and should prompt the clinician to obtain blood ammonia levels, which are significantly elevated in symptomatic patients. This finding should lead to an immediate blood and urine amino acid quantitation, which confirms the presence of argininosuccinic acid in both fluids. In addition, levels of blood citrulline, glutamine, alanine, and lysine may be increased. Argininosuccinic acid lyase may be assayed in cultured fibroblasts, providing the definitive biochemical diagnosis. Urine orotic acid levels are elevated.


Treatment consists of a low protein diet, arginine supplementation to help complete the urea cycle, ammonia scavenging drugs in some cases and supplement carnitine if the patients have a secondary deficiency. Liver transplant offers a partial correction of the enzyme deficiency and improved metabolic status. Patients must avoid fasting and during stressors, like illness, need to supplement with high carbohydrates, non-protein calories to avoid catabolism. In metabolic emergency, acute hemodialysis may be necessary to lower ammonia levels.

NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.


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