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Argininosuccinic Aciduria
Guidance for primary care clinicians receiving a positive newborn screen result
Description
Argininosuccinic aciduria is a urea cycle disorder resulting from deficiency of the enzyme argininosuccinate lyase, disrupting the conversion of argininosuccinate to fumarate and arginine. As with most other urea cycle disorders, it is characterized by hyperammonemia and encephalopathy. However, the common finding of chronic liver disease, trichorrhexis nodosa, and systemic hypertension, often despite optimal metabolic management, is unique to argininosuccinic aciduria. Though commonly considered a disease of severe neonatal onset, late-onset cases in childhood to late adulthood have been reported, typically with a hyperammonemic crisis triggered by an acute infection.
Clinical Characteristics
Initial symptoms of argininosuccinic aciduria may include:
- Poor appetite
- Vomiting
- Irritability
- Seizures
- Lethargy/coma
- Lab findings:
- Hyperammonemia
- Elevated transaminases
- Prolonged PT/PTT
- Elevated citrulline
- Elevated argininosuccinic acid (plasma and urine)
- Episodic hyperammonemia
- Liver disease
- Short, dry, brittle hair (trichorrhexis nodosa)
- Neurocognitive deficits
- Seizures
Incidence
Primary Care Management
Next Steps After a Positive Screen
- Contact the family, inform them of the newborn screening result, and evaluate the infant for clinical symptoms (poor feeding, vomiting, lethargy, tachypnea).
- Immediately consult with Medical Genetics (see OH providers [0]).
- Measure the blood ammonia and initiate emergency treatment or referral if there is evidence of hyperammonemia or clinical symptoms, such as vomiting, refusal of feeds, lethargy, or seizures. See the ACT Sheet for Elevated Citrulline (ACMG) for other immediate steps to take upon notification of a positive screen.
Confirming the Diagnosis
- To confirm the diagnosis of argininosuccinic aciduria, work with Newborn Screening Services (see OH providers [1]).
- Quantitative plasma ammonia and amino acid analysis, urine orotic acid
- Genetic Testing and Counseling (see OH providers [1]) is possible for at-risk family members if both disease-causing mutations of an affected family member have been identified.
If the Diagnosis is Confirmed
- For evaluation and ongoing collaborative management, consult Biochemical Genetics (Metabolics) (see OH providers [0]).
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill. See Argininosuccinic Acid Lyase Deficiency - Information for Parents (newbornscreening.info).
- Assist in implementing and supporting a low-protein diet and arginine and essential amino acid supplements.
- Ammonia scavenging medications (e.g., sodium benzoate or sodium phenylbutyrate) are usually indicated and prescribed by pediatric genetics.
- Regular blood tests to monitor amino acid and ammonia levels may be indicated.
- Immediate hospital admission may be required during episodes of hyperammonemia or illness.
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions. Refer to Early Intervention for Children with Disabilities/Delays (see OH providers [0]) as needed.
Resources
Information & Support
Related Portal Content
After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive
for a newborn condition. Find information about A New Diagnosis; Caring for
Children with Special Health Care Needs; Assistance in Choosing Providers;
Partnering with Healthcare Providers; Top Ten Things to Do After a
Diagnosis.
For Professionals
Argininosuccinic Aciduria (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
Argininosuccinate Lyase Deficiency (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.
For Parents and Patients
Argininosuccinic Aciduria (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources;
from the National Library of Medicine.
Argininosuccinic Acid Lyase Deficiency - Information for Parents (newbornscreening.info)
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.
Tools
Confirmatory Algorithm for Elevated Citrulline (ACMG)
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.
ACT Sheet for Elevated Citrulline (ACMG)
Short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.
Services for Patients & Families in Ohio (OH)
| Service Categories | # of providers* in: | OH | NW | Other states (4) (show) | | NM | NV | RI | UT |
|---|---|---|---|---|---|---|---|---|---|
| Biochemical Genetics (Metabolics) | 1 | 1 | 2 | 3 | 2 | ||||
| Early Intervention for Children with Disabilities/Delays | 3 | 34 | 30 | 13 | 51 | ||||
| Genetic Testing and Counseling | 6 | 6 | 12 | 8 | 11 | ||||
| Medical Genetics | 1 | 2 | 5 | 4 | 7 | ||||
| Newborn Screening Services | 1 | 3 | 2 | 2 | 3 | ||||
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.
Studies
Argininosuccinic Aciduria (ClinicalTrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.
Helpful Articles
PubMed search for argininosuccinic aciduria, last 5 years.
Baruteau J, Diez-Fernandez C, Lerner S, Ranucci G, Gissen P, Dionisi-Vici C, Nagamani S, Erez A, Häberle J.
Argininosuccinic aciduria: Recent pathophysiological insights and therapeutic prospects.
J Inherit Metab Dis.
2019;42(6):1147-1161.
PubMed abstract
Authors & Reviewers
| Author: | Brian J. Shayota, MD, MPH |
| Reviewer: | Nancy C. Rose, MD |
| 2019: update: Chelsea Norman, BS, RDN, CDA; Nicola Longo, MD, Ph.D.R |
| 2012: update: Kimberly Hart, MS, LCGCA |
| 2007: first version: Nicola Longo, MD, Ph.D.A |
Page Bibliography
Baruteau J, Diez-Fernandez C, Lerner S, Ranucci G, Gissen P, Dionisi-Vici C, Nagamani S, Erez A, Häberle J.
Argininosuccinic aciduria: Recent pathophysiological insights and therapeutic prospects.
J Inherit Metab Dis.
2019;42(6):1147-1161.
PubMed abstract
Therrell BL Jr, Lloyd-Puryear MA, Camp KM, Mann MY.
Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions
for research agenda planning.
Mol Genet Metab.
2014;113(1-2):14-26.
PubMed abstract / Full Text