Rare Pulmonology News

Disease Profile

Carbamoyl phosphate synthetase 1 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.

Unknown

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)

Hyperammonemia due to carbamoyl phosphate synthetase 1 deficiency; CPS 1 deficiency; Carbamyl phosphate synthetase (CPS) deficiency

Categories

Congenital and Genetic Diseases; Metabolic disorders; Newborn Screening

Summary

Carbamoyl phosphate synthetase I deficiency (CPS1 deficiency) is a genetic disorder that causes episodes of toxic levels of ammonia in the blood (hyperammonemia). Symptoms include poor feeding, vomiting, lack of energy, low body temperature and weak muscle tone. These usually occur in the first few days of life. High levels of ammonia can lead to complications such as seizures, breathing problems, intellectual disability and coma. CPS1 deficiency is caused by alterations (mutations) in the CPS1 gene and is inherited in an autosomal recessive pattern. Diagnosis is based on symptoms, laboratory testing, and genetic testing. Treatment is aggressive removal of excess ammonia, a protein-limited diet and specific medications.[1][2][3][4][5]

Symptoms

The following list includes the most common signs and symptoms of carbamoyl phosphate synthetase 1 deficiency (CPS1 deficiency). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in CPS1 deficiency.

Symptoms may include:[4][5]

  • Poor feeding
  • Vomiting
  • Progressive lack of energy, irritability, listlessness
  • Low body temperature (hypothermia)
  • Low muscle tone (hypotonia)
  • Complications of breathing (respiration deficiency)
  • Seizures (convulsions)
  • Coma

The symptoms of CPS1 deficiency occur very quickly in the first few days after birth. Without diagnosis and treatment, high levels of ammonia in the blood may result in breathing problems, seizures, intellectual and developmental disability, coma and even death. Children who are successfully treated are still at risk for repeated episodes of high ammonia. Some people with CPS1 deficiency have a milder form and signs and symptoms may be less severe and appear later in life.[1][4][5]

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
Episodic ammonia intoxication
0001951
Hyperammonemia
High blood ammonia levels
0001987
Hypoargininemia
Low blood arginine levels
0005961
Muscular hypotonia
Low or weak muscle tone
0001252
Respiratory insufficiency
Respiratory impairment
0002093
Seizure
0001250
5%-29% of people have these symptoms
Stroke
0001297
Percent of people who have these symptoms is not available through HPO
Ataxia
0001251
Autosomal recessive inheritance
0000007
Cerebral edema
Swelling of brain
0002181
Coma
0001259
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Global developmental delay
0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Irritability
Irritable
0000737
Lethargy
0001254
Low plasma citrulline
0003572
Protein avoidance
0002038
Respiratory alkalosis
0001950
Vomiting
Throwing up
0002013

Cause

Carbamoyl phosphate synthetase I deficiency is caused by genetic alterations (mutations) in the CPS1 gene.[1][2]

Diagnosis

Carbamoyl phosphate synthetase I deficiency (CPS1 deficiency) is diagnosed based on clinical examination, symptoms, biochemical and genetic testing. Some states in the United States screen for CPS1 deficiency as part of newborn screening.[1][2][6]

Testing Resources

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

    Newborn Screening

    • 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.

      Treatment

      Treatment for carbamoyl phosphate synthetase I deficiency (CPS1 deficiency) includes aggressive removal of excess ammonia during an episode of hyperammonemia. CPS1 deficiency is also managed by a special low protein diet that includes supplements and additional medications. Other treatment is based on the symptoms. Seizures can be treated with specific anti-seizure medications. In severe cases, liver transplant may be an option.[1][3][5]

      Specialists who might be involved in the care of someone with CPS1 deficiency include:

      • Nutritionist 
      • Neurologist
      • Genetic specialist

      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 Carbamoyl phosphate synthetase 1 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.

        • 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 Carbamoyl phosphate synthetase 1 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.

            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 Carbamoyl phosphate synthetase 1 deficiency. Click on the link to view a sample search on this topic.

              References

              1. 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/.
              2. Zhang G, Chen Y, Ju H, Bei F, Li J, Wang J, Sun J, Bu J. Carbamoyl phosphate synthetase 1 deficiency diagnosed by whole exome sequencing.. J Clin Lab Anal. Feb 2018; 32(2):e22241. https://www.ncbi.nlm.nih.gov/pubmed/28444906.
              3. Diez-Fernandez C, Häberle J. Targeting CPS1 in the treatment of Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea cycle disorder. J Expert Opin Ther Targets. Apr 2017; 21(4):391-399. https://www.ncbi.nlm.nih.gov/pubmed/28281899.
              4. Fan L, Zhao J, Jiang L, et al. Molecular, biochemical, and clinical analyses of five patients with carbamoyl phosphate synthetase 1 deficiency. J Clin Lab Anal. 2020; 34(4):e23124. https://pubmed.ncbi.nlm.nih.gov/31749211.
              5. Carbamoyl Phosphate Synthetase 1 Deficiency. (CPS1 deficiency). National Organization for Rare Disorders (NORD). Updated 2017; https://rarediseases.org/rare-diseases/carbamoyl-phosphate-synthetase-i-deficiency/.
              6. Díez-Fernández C, Gallego J, Häberle J, Cervera J, Rubio V. The Study of Carbamoyl Phosphate Synthetase 1 Deficiency Sheds Light on the Mechanism for Switching On/Off the Urea Cycle. J Genet Genomics. 2015; 42(5):249-260.

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