Rare Hematology News

Disease Profile

N-acetylglutamate synthase deficiency

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 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

All ages

ageofonset-all.svg

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

no.svg

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

rnn-autosomalrecessive.svg

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.

no.svg

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

no.svg

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.

no.svg

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.

no.svg

Not applicable

no.svg

Other names (AKA)

Hyperammonemia due to N-Acetylglutamate Synthetase Deficiency; NAGS deficiency; NAG synthetase deficiency;

Categories

Congenital and Genetic Diseases; Metabolic disorders; RDCRN

Summary

N-acetylglutamate synthase deficiency (NAGS) is type of metabolic disorder that affects the processing of proteins and removal of ammonia from the body. When proteins are processed by the body, ammonia is formed. Individuals with NAGS are not able to remove ammonia from the body and have symptoms due to toxic levels of ammonia that build up in the blood. NAGS and other similar disorders are a type of metabolic condition known as a urea cycle disorder.[1][2] 

Signs and symptoms in newborns with NAGS may include a lack of energy, unwillingness to eat, seizures, unusual body movements, and poorly controlled breathing or body temperature. Complications may include coma, developmental delay, and learning disability. Some people have a less severe form of the deficiency with earliest symptoms manifesting later in life, particularly following high-protein meals, illness, or other stress. Signs and symptoms may include sudden vomiting, lack of coordination, confusion, and coma. NAGS is caused by mutations in the NAGS gene and is inherited in an autosomal recessive fashion. Treatment may include maintaining a low protein diet and using medications that provide alternative routes to remove ammonia from the body.[1][3]

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
30%-79% of people have these symptoms
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Nausea
0002018
Vomiting
Throwing up
0002013
5%-29% of people have these symptoms
Acute hyperammonemia
0008281
Agitation
0000713
Anxiety
Excessive, persistent worry and fear
0000739
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Coma
0001259
Drowsiness
Sleepy
0002329
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Fatigue
Tired
Tiredness

[ more ]

0012378
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Global developmental delay
0001263
Headache
Headaches
0002315
Hyperalaninemia
Increased blood alanine
Increased serum alanine

[ more ]

0003348
Hyperglutaminemia
High plasma glutamine
0003217
Insomnia
Difficulty staying or falling asleep
0100785
Lethargy
0001254
Loss of consciousness
Passing out
0007185
Mood changes
Moody
0001575
Poor appetite
Decreased appetite
0004396
Poor speech
0002465
Seizure
0001250
1%-4% of people have these symptoms
Ataxia
0001251
Cerebral ischemia
Disruption of blood oxygen supply to brain
0002637
Delirium
0031258
Diarrhea
Watery stool
0002014
Echolalia
Echoing another person's speech
0010529
Encephalopathy
0001298
Hepatomegaly
Enlarged liver
0002240
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Myelodysplasia
0002863
Paraplegia
Leg paralysis
0010550
Polyneuropathy
Peripheral nerve disease
0001271
Psychotic episodes
0000725
Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

0002098
Reye syndrome-like episodes
0006582
Stereotypy
Repetitive movements
Repetitive or self-injurious behavior

[ more ]

0000733
Stroke
0001297
Percent of people who have these symptoms is not available through HPO
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness

[ more ]

0000718
Autosomal recessive inheritance
0000007
Confusion
Disorientation
Easily confused
Mental disorientation

[ more ]

0001289
Hyperammonemia
High blood ammonia levels
0001987
Increased level of L-glutamic acid in blood
0410068

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

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    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

    • GeneReviews provides a current, expert-authored, peer-reviewed, full-text article urea cycle disorders in general that you may find helpful. GeneReview articles describe the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
    • The NORD Physician Guide for N-acetylglutamate synthase deficiency 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.

      • Carglumic acid(Brand name: Carbaglu) Manufactured by Orphan Europe SARL
        FDA-approved indication: As an adjunctive therapy for the treatment of acute hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS) and as manitenance therapy for chronic hyperammonemia due to NAGS deficiency.
        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 N-acetylglutamate synthase deficiency. 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 National Urea Cycle Disorders Foundation, a nonprofit organization that supports urea cycle disorders, offers information on urea cycle disorders, including N-acetylglutamate synthase deficiency

          In-Depth Information

          • 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 N-acetylglutamate synthase deficiency. Click on the link to view a sample search on this topic.

            References

            1. N-acetylglutamate synthase deficiency. Genetics Home Reference. October 2006; https://ghr.nlm.nih.gov/condition=nacetylglutamatesynthasedeficiency.
            2. What is a Urea Cycle Disorder?. National Urea Cyle Disorders Foundation. https://www.nucdf.org/ucd.htm. Accessed 4/12/2017.
            3. Mew NA, Lanpher BC, Gropman A, Chapman KA, Simpson KL, Summar ML. Urea Cycle Disorders Overview. GeneReviews. April 9, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1217/.

            Rare Hematology News