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Argininemia

Disorder Category

an amino acid (urea cycle) disorder

Screening

Finding

elevated arginine

Tested By

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

Names

Argininemia

Arginase deficiency (ARG 1)

Hyperargininemia

ICD-9

270.6, Disorder of urea cycle metabolism

Overview

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.

Prevalence

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

Inheritance

autosomal recessive

Prenatal Testing

DNA testing by amniocentesis or CVS. Enzyme testing by fetal blood sampling (arginase is expressed in red cells).

Other Testing

Genetic testing is possible if the mutations in both parental carriers are known.

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, and
  • 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, and
  • 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 on positive screening test

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 info 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): Medical Genetics, (801-231-3599); See also Services below. A dietician may work with the family to devise an optimal approach to dietary management.

Resources

Information & Support

For Professionals

Argininemia info for professionals (STAR-G)
On the Screening, Technology and Research in Genetics (STAR-G) site, one of a series of Disorder Fact Sheets for Professionals; structured list of information about the condition, with links to more information.

ACT Sheet for Argininemia (ACMG) (PDF Document 348 KB)
Developed by the American College of Medical Genetics), includes recommended responses to positive newborn screening test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.

ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.

Argininemia Acute Illness Protocol (NECMP)
A guideline for healthcare professionals treating the sick infant/child who has previously been diagnosed 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 (GeneReviews)
Excellent review by Stephen Cederbaum, MD and Eric A Crombez, MD, including clinical description, differential, management, genetic counseling, molecular genetics, and a bibliography.

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

Utah Newborn Screening Program
The site provides information and statistics about the program and related legislation, training for practices, and the conditions screened for.

For Parents and Patients

Argininemia info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) site, providing information for parents about argininemia and links to other sites including parent support groups.

Argininemia (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference site.

National Urea Cycle Disorders Foundation
The National Urea Cycle Disorders Foundation, a 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.

National Newborn Screening & Genetics Resource Center
Provides information for families and professionals about genetic screening; links to support and advocacy groups; links to state genetic contacts; newsletters; fact sheets; data reports; publications; and more.

Services

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

Newborn Screening Programs

Utah Newborn Screening Program, more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening

Pediatric Medical Genetics

See all Pediatric Medical Genetics services providers (3) in our database.

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

Helpful Articles

PubMed search for articles on argininemia in the 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

Authors

Reviewing Author: Nicola Longo MD, PhD, 3/2007
Compiled and edited by: Alfred Romeo RN, PhD, 3/2007
Content Last Updated: 9/2010