Disorder Category

An amino acidemia



Elevated arginine

Tested By

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



Arginase deficiency (ARG 1)



270.6, Disorder of urea cycle metabolism


One of the known urea cycle disorders, all characterized by hyperammonemia and encephalopathy. A deficiency, usually near complete absence, of activity of arginase, blocks the final step of the cycle. Unlike other urea cycle defects, argininemia usually presents after 1 year of age with progressive spastic paraparesis, developmental delays, seizures that become progressively harder to control, and sometimes acquired microcephaly and short stature.


Approximately 1 in 300,000 live births [Argininemia - Information for Professionals (STAR-G)]; possibly more frequent among French Canadians and in parts of Japan [Argininemia (GeneReviews)]


Autosomal recessive

Prenatal Testing

Genetic testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified. Enzyme testing by fetal blood sampling (arginase is expressed in red cells).

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 a serious hyperammonemic episode, clinical and developmental outcome may be improved. Without treatment, symptoms may begin shortly after birth or as late as a few years of age, but most affected children will show developmental delays at about 1 year of age followed by progressive spasticity even in the absence of acute episodes of hyperammonemia. Acute symptoms may occur during prolonged fasting, periods of increased energy demands (fever, stress, lack of sleep), and after meals high in protein.

Initial signs and symptoms may include:
  • poor appetite
  • illness or fussiness following high-protein feedings
  • vomiting
  • irritability
  • lethargy
  • lab findings:
    • elevated arginine
    • elevated urine orotic acid
    • hyperammonemia (though usually not as high as in other urea cycle defects)
Subsequent signs and symptoms may include:
  • poor growth
  • muscle weakness
  • spasticity
  • microcephaly
  • seizures
  • mental retardation
  • death (up to 75% live long, though handicapped, lives)

Treatment includes a low protein diet 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

Plasma amino acid analysis and urine orotic acid. Enzyme assay on red blood cells can be used to confirm the diagnosis. DNA testing is used for final diagnostic confirmation.

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 Argininemia - Information for Parents (STAR-G));
  • Assist in implementation and support of a low protein diet;
  • Sodium benzoate or phenylbutyrate therapy help reduce arginine and ammonia levels;
  • Periodic monitoring of amino acid and ammonia levels is indicated;
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
  • Periodic Botox injections and heel cord lengthening can improve spasticity in these patients.

Specialty Care Collaboration

Initial consultation and ongoing collaboration with the following service(s): Pediatric Medical Genetics , (801-213-3599); See also Services below. A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family.


Information & Support

For Professionals

Argininemia Acute Illness Protocol (NECMP)
Guideline for clinicians treating the sick infant or child with argininemia; 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.

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

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

Argininemia (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 Argininemia (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; National Library of Medicine and the Genetic Alliance.

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.

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

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

Argininemia - 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 Argininemia (ACMG) (PDF Document 348 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithms for Argininemia (ACMG) (PDF Document)
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 argininemia in children, last 5 years.

Scaglia F, Lee B.
Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency.
Am J Med Genet C Semin Med Genet. 2006;142C(2):113-20. PubMed abstract


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