Home > Newborn Disorders > Argininosuccinic aciduria
Argininosuccinic aciduria
Names
Argininosuccinic aciduria
Argininosuccinic acid lyase deficiency (ASAL)
Argininosuccinase deficiency
ASL deficiency
Overview
One of the known urea cycle disorders, all 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 in being able to cause chronic liver disease or (in very mild forms), isolated mental retardation.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, and
- lab findings:
- hyperammonemia,
- elevated transaminases
- prolonged PT/PTT
- elevated citrulline,
- elevated glutamine,
- elevated argininosuccinic acid, and
- elevated urine orotic acid.
Subsequent symptoms may include:
- poor growth/failure to thrive;
- liver enlargement;
- muscle weakness;
- short, dry, brittle hair (trichorrhexis nodosa);
- cerebral edema;
- seizures;
- mental retardation; and
- 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 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;
- Measure the blood ammonia and provide emergency treatment/referral if there is evidence of illness - vomiting, hypotonia,
seizures, or signs of liver disease (see the ACT Sheet for elevated citrulline (ACMG)
(
346 KB)
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): Medical Genetics, (801-231-3599); 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) 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.Resources
Information & Support
For Professionals
Argininosuccinic aciduria info for professionals (STAR-G)
On the Screening, Technology and Research in Genetics (STAR-G) program, 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 elevated citrulline (ACMG)
( 346 KB)
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.
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.
Argininosuccinic Aciduria Acute Illness Protocol
A guideline for healthcare professionals treating the sick infant/child who has previously been diagnosed with arginnocuccinic
acidemia; 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.
Resources for argininosuccinic aciduria (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
Argininosuccinic aciduria (OMIM)
Extensive review of the literature, including clinical features and genetics, 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 and Patients
Argininosuccinic aciduria info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, providing information for parents about argininosuccinic
aciduria and links to other sites including parent support groups.
Argininosuccinic aciduria (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
ASA Kids
A support group for those dealing with Argininosuccinic Aciduria.
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
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 on argininosuccinic aciduria in the last 10 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
Authors
| Reviewing Author: | Nicola Longo MD, PhD, 3/2007 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 9/2010 |