
			Screening & Prevention

Screening and Prevention Intro
Developmental Screening
Infant Social-Emotional Screening
Maternal Depression Screening
Newborn Screening
- Amino Acid Disorders
- Endocrine Disorders
  - Congenital adrenal hyperplasia
  - Congenital hypothyroidism
- Fatty Acid Oxidation Disorders
- Galactosemias
  - Galactosemia
- Hemoglobinopathies
  - Sickle cell disease
- Organic Acidemias

Argininosuccinic aciduria

Screening

Tested By

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

Names

Argininosuccinic acid lysae deficiency (ASAL)

Argininosuccinase deficiency

ASL deficiency

ICD-9

270.6, Disorder of urea cycle metabolism

One of 5 known urea cycle disorders, all characterized by hyperammonemia, encephalopathy, and respiratory alkalosis. The enzyme argininosuccinic acid lyase is deficient, blocking conversion of argininosuccinate to fumarate and arginine.

Prevalence

about 1/70,000 live births

Inheritance

autosomal recessive

Prenatal Testing

DNA and enzyme testing by amniocentesis or CVS.

Other Testing

DNA testing may be done if carrier mutations are known.

Clinical Characteristics

With treatment before hyperammonemic crises, normal mental and physical development is possible. 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, and
lab findings:
- hyperammonemia,
- elevated citrulline, and
- elevated argininosuccinic acid.

Subsequent symptoms may include:

poor growth/failure to thrive;
liver enlargement;
muscle weakness;
spasticity;
short, dry, brittle hair (trichorrhexis nodosa);
cerebral edema;
seizures;
mental retardation; and
death.

Follow-up on positive screening test

Quantitative plasma ammonia and amino acid analysis, urine orotic acid.

Primary care management

Upon notification of the + screen

Contact the family and evaluate the infant for poor feeding, vomiting, lethargy, tachypnea;
Measure the blood ammonia and provide emergency treatment/referral if there is evidence of illness - vomiting, hypotonia, tachypnea, seizures, or signs of liver disease (see the ACT Sheet for Argininosuccinic aciduria from ACMG (pdf 62kb) below for additional information);
To confirm the diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
For evaluation and ongoing collaborative management, consult the following service(s): Metabolic Clinic, (801-585-2457); See also Services below;

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 info 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) may be 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 Management

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.

Resources

Links

For Professionals

Argininosuccinic aciduria 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 Argininosuccinic aciduria from ACMG (pdf 62kb)
Developed by the American College of Medical Genetics (ACMG), 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.

ACMG ACT Sheets and Confirmatory Algorithms
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.

Argininosuccinic aciduria Emergency Protocol
A protocol for management of the patient with a positive screen for argininosuccinic aciduria, from the New England Consortium of Metabolic Programs.

Argininosuccinic aciduria, OMIM
Extensive review of the literature, including clinical features and gene therapy, from the Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University, providing technical information for providers on genetic disorders, links to MEDLINE, and links to other scientific information and sites.

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

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

Argininosuccinic aciduria, Genetics Home Reference
xcellent, 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.

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

Helpful Articles

PubMed search for articles on argininosuccinic aciduria in the last 5 years.

Authors

Reviewing Author:

Nicola Longo MD, PhD, 3/2007

Compiled and edited by:

Alfred Romeo RN, PhD, 3/2007

Content Last Updated:

3/2008

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Argininosuccinic aciduria

Disorder Category

Screening

Finding

Tested By

Names

ICD-9

Overview

Prevalence

Inheritance

Prenatal Testing

Other Testing

Clinical Characteristics

Follow-up on positive screening test

Primary care management

Upon notification of the + screen

If the diagnosis is confirmed

Specialty Care Management

Resources

Links

For Professionals

For Parents

Services

Newborn Screening Programs

Pediatric Genetics

Helpful Articles

Authors