Argininosuccinic Aciduria

Other Names

Argininosuccinic acid lyase deficiency (ASAL)

Argininosuccinase deficiency

ASL deficiency

Diagnosis Coding

E72.22, arginosuccinic aciduria

Disorder Category

An amino acidemia



Elevated citrulline and argininosuccinic acid

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA


A urea cycle disorder characterized by hyperammonemia and encephalopathy. The enzyme argininosuccinic acid lyase is deficient, blocking conversion of argininosuccinate to fumarate and arginine. This disease differs from other urea cycle defects because it causes chronic liver disease or isolated mental retardation (in very mild forms).


Approximately 1 in 70,000 live births [Brusilow: 2013]


Autosomal recessive

Prenatal Testing

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified. Enzyme testing possible by amniocentesis or CVS.

Other Testing

Genetic testing is possible for at-risk family members if both disease causing mutations of an affected family member have been identified.

Clinical Characteristics

With treatment before hyperammonemic crises, normal mental and physical development is possible. The results of newborn screening can return after the infant is already symptomatic. Without treatment, symptoms usually begin a few days after birth. Less severe variants may present in childhood. Acute symptoms may occur during prolonged fasting, periods of increased energy demands (fever, stress, lack of sleep), and after meals high in protein.

Initial symptoms may include:
  • Poor appetite
  • Vomiting
  • Irritability
  • Seizures
  • Lethargy
  • Lab findings:
    • Hyperammonemia
    • Elevated transaminases
    • Prolonged PT/PTT
    • Elevated citrulline
    • Elevated glutamine
    • Elevated argininosuccinic aci
    • Elevated urine orotic acid
(NOTE: Some laboratories have difficulties in identifying argininosuccinic acid in plasma and urine amino acids might prove valuable in such cases)
Subsequent symptoms may include:
  • Poor growth/failure to thrive
  • Liver enlargement
  • Muscle weakness
  • Short, dry, brittle hair (trichorrhexis nodosa)
  • Cerebral edema
  • Seizures
  • Mental retardation
  • Death

Treatment includes a low protein diet, arginine supplementation and the use of sodium benzoate or phenylbutyrate to remove the nitrogen load using an alternative mechanism. Patients should be monitored periodically with laboratory tests to verify adequacy of amino acid concentration maintaining normal ammonia levels.

Follow-up Testing after Positive Screen

Quantitative plasma ammonia and amino acid analysis, urine orotic acid

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Argininosuccinic Aciduria - Information for Parents (STAR-G) below);
  • Assist in implementation and support of a low protein diet and provision of arginine and essential amino acid supplements;
  • Ammonia scavenging medications (e.g. sodum benzoate or sodium phenylbutyrate) are usually indicated;
  • Regular blood tests to monitor amino acid and ammonia levels may be indicated;
  • Immediate hospital admission may be required to help reduce ammonia levels during episodes of hyperammonemia;
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.

Specialty Care Collaboration

Initial consultation and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family.


Information & Support

For Professionals

Argininosuccinic Aciduria Acute Illness Protocol (NECMP)
Guideline for clinicians treating the sick infant/child who has previously been diagnosed with argininosuccinic acidemia (ASA); developed under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and Professor of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs. Click pdf to view the complete protocol.

Argininosuccinic Aciduria - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

Argininosuccinic Aciduria (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Argininosuccinate Lyase Deficiency (GeneReviews)
An expert-authored, peer-reviewed, current disease description that applies genetic testing to diagnosis and management information for the condition; National Center for Biotechnology Information, U.S. National Library of Medicine.

Resources for Argininosuccinic Aciduria (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.

Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.

Newborn Screening Information for Clinicians (NNSGRC)
Fact sheets, data reports, publications ,and information for clinicians about genetic screening that includes links to state genetic contacts; National Newborn Screening & Global Resource Center.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

Orphanet is a consortium involving over 40 countries and coordinated in France to provide a portal for information about rare diseases and orphan drugs.

Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.

For Parents and Patients

Argininosuccinic Aciduria (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.

Argininosuccinic Aciduria - Information for Parents (STAR-G)
A factsheet, written by a genetic counselor and reviewed by genetic specialists, for families who have received an initial diagnosis of a newborn disorder; Screening, Technology, and Research in Genetics.

National Urea Cycle Disorders Foundation
This non-profit organization provides support services and information for families; medical lectures on urea cycle disorders; nutrition and medication resources; and information about events and conferences.

Baby's First Test (Genetic Alliance)
A clearinghouse for newborn screening information. Provides resources about screening at the local, state, and national levels and ways for people to share their viewpoints and questions about newborn screening.

Newborn Screening Information For Families (NNSGRC)
Information for families about genetic screening; links to support groups, advocacy groups, and state genetic contacts; newsletters; factsheets; data reports; and publications; National Newborn Screening and Global Resource Center.

Utah Parent Center
A non-profit organization that provides training, information, referral, and assistance to parents of children and youth with all disabilities including physical, mental, hearing, vision, learning, behavioral, and emotional. Staff consists primarily of parents of children and youth with disabilities.

Center for Parent Information and Resources (DOE)
A large resource library related to children with disabilities. Parent Centers in every state provide training to parents of children with disabilities. Lists local conferences, support groups, advocacy tips, and suggestions for finding schools and other local services; Department of Education, Office of Special Education.


ACT Sheet for Elevated Citrulline (ACMG) (PDF Document 346 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithms for Elevated Citrulline (ACMG)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American College of Medical Genetics.


Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for argininosuccinic aciduria, last 5 years.

Mercimek-Mahmutoglu S, Moeslinger D, Häberle J, Engel K, Herle M, Strobl MW, Scheibenreiter S, Muehl A, Stöckler-Ipsiroglu S.
Long-term outcome of patients with argininosuccinate lyase deficiency diagnosed by newborn screening in Austria.
Mol Genet Metab. 2010;100(1):24-8. PubMed abstract


Reviewing Authors: Kimberly Hart, MS, LCGC - 6/2012
Nicola Longo, MD, PhD - 3/2007
Compiled and edited by: Alfred Romeo, RN, PhD - 4/2012
Content Last Updated: 6/2012

Page Bibliography

Brusilow S, Horwich A.
Urea cycle enzymes. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, eds.
The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID); (2013) Accessed on 7-22-15.