Arginase Deficiency

Other Names



Diagnosis Coding

E72.21, argininemia

Disorder Category

An amino acidemia



Elevated arginine

Tested By

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


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. On rare occasions, it presents early in life, as with other urea cycle defects.


The prevalence of arginase deficiency is unknown. The incidence of Arginase deficiency is 1:950,000. The incidence of all urea cycle disorders is 1:35,000. In the United States, that equates to about 113 new patients per year. [Summar: 2013]


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)
    • Elevated guanidinoacetate
Subsequent signs and symptoms may include:
  • Poor growth
  • Muscle weakness
  • Spasticity
  • Microcephaly
  • Seizures
  • Intellectual disability
  • 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 Genetics (see NW providers [1]). A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family.


Information & Support

For Professionals

Arginase Deficiency (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 (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

Argininemia (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

Resources for Argininemia (Disease InfoSearch)
Compilation of information, articles, and links to support; from Genetic Alliance.

For Parents and Patients

Arginase deficiency (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Argininemia - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by genetic specialists, for families who have received a diagnosis of arginase deficiency; Screening, Technology, and Research in Genetics.

National Urea Cycle Disorders Foundation
Support and information that includes medical lectures on urea cycle disorders, nutrition and medication resources, and information about events and conferences.

Baby's First Test (Genetic Alliance)
Clearinghouse for local, state, and national newborn screening education, programs, policies, and resources. Also, provides many ways for people to connect and share their viewpoints and questions about newborn screening; supported by the U.S. Department of Health and Human Services.

Center for Parent Information and Resources (DOE)
Parent centers in every state provide training to parents of children with disabilities and provide information about special education, transition to adulthood, health care, support groups, local conferences and other federal, state, and local services. See the "Find Your Parent Center Link" to find the parent center in your state; 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.

Services for Patients & Families Nationwide (NW)

Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG).

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.


Arginase Deficiency (
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

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 / Full Text

Therrell BL, Currier R, Lapidus D, Grimm M, Cederbaum SD.
Newborn screening for hyperargininemia due to arginase 1 deficiency.
Mol Genet Metab. 2017;121(4):308-313. PubMed abstract

Huemer M, Carvalho DR, Brum JM, Ünal Ö, Coskun T, Weisfeld-Adams JD, Schrager NL, Scholl-Bürgi S, Schlune A, Donner MG, Hersberger M, Gemperle C, Riesner B, Ulmer H, Häberle J, Karall D.
Clinical phenotype, biochemical profile, and treatment in 19 patients with arginase 1 deficiency.
J Inherit Metab Dis. 2016;39(3):331-340. PubMed abstract

Authors & Reviewers

Initial publication: March 2007; last update/revision: September 2018
Current Authors and Reviewers:
Author: Nicola Longo, MD, Ph.D.
Reviewer: Kimberly Hart, MS, LCGC

Page Bibliography

Summar ML, Koelker S, Freedenberg D, Le Mons C, Haberle J, Lee HS, Kirmse B.
The incidence of urea cycle disorders.
Mol Genet Metab. 2013;110(1-2):179-80. PubMed abstract / Full Text