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Disease Profile

Argininosuccinic aciduria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

All ages

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ICD-10

E72.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Arginino succinase deficiency; Inborn error of urea synthesis, arginino succinic type; Urea cycle disorder, arginino succinase type;

Categories

Congenital and Genetic Diseases; Metabolic disorders; RDCRN

Summary

Argininosuccinic aciduria is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia. Argininosuccinic aciduria usually becomes evident in the first few days of life. An infant with argininosuccinic aciduria may be lacking in energy (lethargic) or unwilling to eat, and have poorly controlled breathing rate or body temperature. Some babies with this disorder experience seizures or unusual body movements, or go into a coma. Complications from argininosuccinic aciduria may include developmental delay, intellectual disability, progressive liver damage, skin lesions, and brittle hair. The condition is caused by mutations in the ASL gene and is inherited in an autosomal recessive pattern.[1] Long-term management includes dietary restriction of protein and supplementation with arginine. Acute crises may be treated by discontinuing oral protein intake, supplementing oral intake with intravenous lipids and/or glucose, and use of intravenous arginine and nitrogen scavenging therapy. If ammonia levels do not normalize, hemodialysis may be necessary.[2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

0003355
Hyperglutaminemia
High plasma glutamine
0003217
Hypoargininemia
Low blood arginine levels
0005961
Oroticaciduria
High urine orotic acid levels
0003218
30%-79% of people have these symptoms
Ataxia
0001251
EEG abnormality
0002353
Hyperammonemia
High blood ammonia levels
0001987
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Short stature
Decreased body height
Small stature

[ more ]

0004322
5%-29% of people have these symptoms
Abnormal hair quantity
0011362
Trichorrhexis nodosa
0009886
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Brittle hair
0002299
Cerebral edema
Swelling of brain
0002181
Coma
0001259
Dry hair
0011359
Elevated serum aspartate aminotransferase
0031956
Episodic ammonia intoxication
0001951
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties in infancy
0008872
Global developmental delay
0001263
Hepatic fibrosis
0001395
Hepatomegaly
Enlarged liver
0002240
Irritability
Irritable
0000737
Lethargy
0001254
Neonatal onset
0003623
Protein avoidance
0002038
Respiratory alkalosis
0001950
Seizure
0001250
Vomiting
Throwing up
0002013

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Newborn Screening

    • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
    • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
    • The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.
    • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
    • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

      Treatment

      The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

      Management Guidelines

      • The NORD Physician Guide for Argininosuccinic aciduria was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors. The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition.
      • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

        FDA-Approved Treatments

        The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

        • Glycerol phenylbutyrate(Brand name: Ravicti) Manufactured by Horizon Pharma, Inc.
          FDA-approved indication: Use as a nitrogen-binding adjunctive therapy for chronic management of adult and pediatric patients at least 2 months of age with urea cycle disorders (UCDs) that cannot be managed by dietary protein restriction and/or amino acid supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (eg, essential amino acids, arginine, citrulline, protein-free calorie supplements).
          National Library of Medicine Drug Information Portal

        Organizations

        Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

        Organizations Supporting this Disease

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

          • MedlinePlus.gov provides more information on urea cycle disorders in general. MedlinePlus is a Web site designed by the National Library of Medicine to help you research your health questions.
          • Genetics Home Reference (GHR) contains information on Argininosuccinic aciduria. This website is maintained by the National Library of Medicine.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
          • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Argininosuccinic aciduria. Click on the link to view a sample search on this topic.

              References

              1. Argininosuccinic aciduria. Genetics Home Reference (GHR). 2007; https://www.ghr.nlm.nih.gov/condition/argininosuccinic-aciduria. Accessed 4/29/2011.
              2. Nagamani SCS, Erez A, Lee B. Argininosuccinate Lyase Deficiency. GeneReviews. 2011; https://www.ncbi.nlm.nih.gov/books/NBK51784/. Accessed 4/29/2011.