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PubMed This is a summary of 20 peer-reviewed journal articles Updated
Biochemical Genetics

Understanding Argininosuccinic Aciduria (ASA): First Steps

At a Glance

Argininosuccinic Aciduria (ASA) is a genetic disorder where the body cannot properly process protein, causing toxic ammonia buildup in the blood. Treatment requires lifelong care with a strict low-protein diet, specialized medications, and close monitoring by a multidisciplinary metabolic team.

Receiving a diagnosis of Argininosuccinic Aciduria (ASA) is often an overwhelming and unexpected experience. It is important to know that while this condition is complex, it is a well-recognized medical disorder with established management strategies and dedicated teams of specialists ready to support you and your family [1][2].

Understanding ASA

ASA is a rare inherited condition that interferes with how the body processes protein. Specifically, it is a urea cycle disorder (UCD)—the second most common type of UCD [3][4]. In a healthy body, the urea cycle converts excess nitrogen (a toxic byproduct of protein digestion) into urea, which is then safely removed through urine. In individuals with ASA, a specific enzyme called argininosuccinate lyase (ASL) is missing or not working correctly [5][6].

This enzyme deficiency causes two primary issues:

  1. Ammonia Buildup: Nitrogen that should have been turned into urea instead builds up in the blood as ammonia (hyperammonemia), which is highly toxic to the brain [5][7].
  2. Nitric Oxide Deficiency: The ASL enzyme is also responsible for helping the body produce nitric oxide, a molecule essential for healthy blood vessels and nervous system function [8][4].

The Role of Genetics

ASA is caused by mutations in the ASL gene [5]. It is an autosomal recessive disorder, meaning a person must inherit two changed copies of the gene (one from each parent) to have the condition [5][6]. Parents are typically “carriers,” meaning they have one changed gene and one healthy gene, and usually show no symptoms themselves.

Two Main Forms of ASA

While the genetic cause is the same, ASA can appear at different times in a person’s life:

  • Neonatal-Onset: This is the most severe form, typically appearing within the first few days of life [5]. Newborns may become extremely sleepy, have trouble feeding, or experience vomiting as ammonia levels rise quickly [9][10].
  • Late-Onset: This form can appear during childhood, adolescence, or even adulthood [7][10]. It is often triggered by “metabolic stress,” such as a common virus, suddenly consuming high amounts of protein, or prolonged fasting [7][11]. Some individuals with late-onset ASA may not be detected by standard newborn screenings [12].

Three Stabilizing Facts

In the wake of a diagnosis, these three facts provide a foundation for care:

  1. Management is Precise: Doctors use specific laboratory tests to monitor levels of argininosuccinic acid and ammonia [13][14]. Treatments often include a specialized low-protein diet and medications that provide an “alternative route” for nitrogen to leave the body [15][16].
  2. A Dual Approach to Health: Your medical team will focus on more than just ammonia. Because ASA also affects nitric oxide, they will proactively monitor for long-term health factors like blood pressure and liver health [8][17].
  3. You Have a Specialist Team: You are not alone in managing this. Individuals with ASA are cared for by a multidisciplinary metabolic team, which typically includes metabolic doctors (biochemical geneticists), specialized dietitians, and nurses [1][2]. Close coordination with this team is the most effective way to protect health and neurological development [18][1].

In some cases, your team may eventually discuss liver transplantation. While it is a major procedure, it can prevent future metabolic crises and significantly improve the quality of life for many individuals with ASA [19][20].

Common questions in this guide

What is argininosuccinic aciduria (ASA)?
ASA is a rare inherited urea cycle disorder where the body cannot properly break down protein. This leads to a dangerous buildup of ammonia in the blood, which can cause severe neurological issues if left untreated.
What causes Argininosuccinic Aciduria?
ASA is caused by inherited mutations in the ASL gene. A person must inherit two altered copies of the gene, one from each parent, to develop the condition. Parents who carry only one altered gene usually do not have symptoms.
What are the early symptoms of neonatal-onset ASA?
In newborns, symptoms typically appear within the first few days of life as ammonia levels rise quickly. Warning signs include extreme sleepiness, poor feeding, and vomiting.
How is argininosuccinic aciduria treated?
Treatment primarily involves a specialized low-protein diet and specific medications that help remove excess nitrogen from the body. In some severe cases, a liver transplant may be considered to prevent future metabolic crises.
What should I do if my child with ASA gets sick?
Common viruses, fevers, or the inability to keep food down can trigger a dangerous metabolic crisis. It is essential to work with your metabolic team to establish a specific 'sick day protocol' to manage illness and prevent ammonia buildup.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Was the diagnosis made through a newborn screening or because of specific symptoms?
  2. 2.Who are the members of our multidisciplinary metabolic team, and how do we reach them in an emergency?
  3. 3.Can you explain the specific ASL gene mutations involved and what they might mean for the severity of the condition?
  4. 4.What is our 'sick day protocol' for when there is a fever or inability to keep food down?
  5. 5.How will we monitor for both ammonia levels and signs of nitric oxide deficiency, like high blood pressure?
  6. 6.Is a liver transplant something we should be learning about for the future?

Questions For You

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References

References (20)
  1. 1

    Challenges in the diagnosis and management of urea cycle disorders in Romanian children.

    Pop TL, Grama A, Miclea D, et al.

    Medicine and pharmacy reports 2021; (94(Suppl No 1)):S36-S39 doi:10.15386/mpr-2226.

    PMID: 34527907
  2. 2

    Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision.

    Häberle J, Burlina A, Chakrapani A, et al.

    Journal of inherited metabolic disease 2019; (42(6)):1192-1230 doi:10.1002/jimd.12100.

    PMID: 30982989
  3. 3

    Low prevalence of argininosuccinate lyase deficiency among inherited urea cycle disorders in Korea.

    Kim D, Ko JM, Kim YM, et al.

    Journal of human genetics 2018; (63(8)):911-917 doi:10.1038/s10038-018-0467-2.

    PMID: 29773863
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    Natural history of epilepsy in argininosuccinic aciduria provides new insights into pathophysiology: A retrospective international study.

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    Epilepsia 2023; (64(6)):1612-1626 doi:10.1111/epi.17596.

    PMID: 36994644
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    [Genetic diagnosis of a Chinese pedigree affected with neonatal argininosuccinic aciduria].

    Li W, Li H

    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2019; (36(9)):926-929 doi:10.3760/cma.j.issn.1003-9406.2019.09.018.

    PMID: 31515792
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    Clinical and genetic analysis of five Chinese patients with urea cycle disorders.

    Zheng Z, Lin Y, Lin W, et al.

    Molecular genetics & genomic medicine 2020; (8(7)):e1301 doi:10.1002/mgg3.1301.

    PMID: 32410394
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    Late-onset argininosuccinic aciduria associated with hyperammonemia triggered by influenza infection in an adolescent: A case report.

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    Molecular genetics and metabolism reports 2020; (24()):100605 doi:10.1016/j.ymgmr.2020.100605.

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    Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension.

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    American journal of human genetics 2018; (103(2)):276-287 doi:10.1016/j.ajhg.2018.07.008.

    PMID: 30075114
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    Late-onset argininosuccinic aciduria in a 72-year-old man presenting with fatal hyperammonemia.

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    JIMD reports 2021; (62(1)):44-48 doi:10.1002/jmd2.12251.

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    The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation.

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    Nonhepatic hyperammonemic encephalopathy due to undiagnosed urea cycle disorder.

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    Argininosuccinic Acid Lyase Deficiency Missed by Newborn Screen.

    Ganetzky RD, Bedoukian E, Deardorff MA, Ficicioglu C

    JIMD reports 2017; (34()):43-47 doi:10.1007/8904_2016_2.

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    Rapid quantification of underivatized alloisoleucine and argininosuccinate using mixed-mode chromatography with tandem mass spectrometry.

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    Determination of amino acid profile for argininosuccinic aciduria disorder using High-Performance Liquid Chromatography with fluorescence detection.

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    Urea Cycle Related Amino Acids Measured in Dried Bloodspots Enable Long-Term In Vivo Monitoring and Therapeutic Adjustment.

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    Inborn Errors of Metabolism with Hyperammonemia: Urea Cycle Defects and Related Disorders.

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    Brain-lung-thyroid syndrome in a neonate with argininosuccinate lyase deficiency.

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    Positive Clinical, Neuropsychological, and Metabolic Impact of Liver Transplantation in Patients With Argininosuccinate Lyase Deficiency.

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This page provides educational information about Argininosuccinic Aciduria (ASA) and its management. It does not replace professional medical advice from your metabolic team or biochemical geneticist.

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