Carbamoyl phosphate synthetase 1 deficiency

Title

Other Names:

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

This disease is grouped under:

Urea cycle disorders

Summary 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]

Last updated: 4/21/2020

Symptoms 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]

Last updated: 4/21/2020

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.

Showing of 21 |

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

Showing of 21 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 7/1/2020

Cause Cause

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

Last updated: 4/21/2020

Inheritance Inheritance

Carbamoyl phosphate synthetase I deficiency is inherited in an autosomal recessive manner.^[1]^[4] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must be altered to have the condition.

People with autosomal recessive conditions inherit one copy from each of their parents. The parents, who each have one gene alteration, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Last updated: 4/21/2020

Diagnosis 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]

Last updated: 4/21/2020

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

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

Last updated: 4/21/2020

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

Statistics Statistics

The incidence of carbamoyl phosphate synthetase 1 deficiency is estimated to be between 1/50,000 and 1/300,000.^[6] The exact number of people born with this condition is unknown.

Last updated: 4/21/2020

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses mainly include other urea cycle disorders and organic acidurias. Amino acid profiles will distinguish CPS1D from argininosuccinic aciduria, citrullinemia type I and arginase deficiency while orotic acid in urine should help to distinguish from ornithine transcarbamylase deficiency. Another more recent differential diagnosis is hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnoses mainly include other urea cycle disorders and organic acidurias. Amino acid profiles will distinguish CPS1D from argininosuccinic aciduria, citrullinemia type I and arginase deficiency while orotic acid in urine should help to distinguish from ornithine transcarbamylase deficiency. Another more recent differential diagnosis is hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency.

Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Patient Registry

The Urea Cycle Disorders Consortium is a team of doctors, nurses, research coordinators, and research labs throughout the US, working together to improve the lives of people with Urea Cycle Disorders. The Urea Cycle Disorders Consortium maintains a registry for patients who wish to be contacted about clinical research opportunities.
For more information on the registry see: !LINK!

Organizations 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

Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org
National Urea Cycle Disorders Foundation
75 South Grand Avenue
Pasadena, CA 91105
Toll-free: 800-38-NUDCF (386-8233)
Telephone: +1-626-578-0833
E-mail: info@nucdf.org
Website: http://www.nucdf.org

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The HealthWell Foundation provides financial assistance for underinsured patients living with chronic and life-altering conditions. They offer help with drug copayments, deductibles, and health insurance premiums for patients with specific diseases. The disease fund status can change over time, so you may need to check back if funds are not currently available.

Education Resources

The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

Learn More 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

Genetics Home Reference (GHR) contains information on Carbamoyl phosphate synthetase 1 deficiency. This website is maintained by the National Library of Medicine.
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.
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.

News & Events News & Events

News

NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

GARD Answers GARD Answers

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Have a question? Contact a GARD Information Specialist.

References References

Mew NA, Lanpher BC, Gropman A, Chapman KA, Simpson KL, Summar ML. Urea Cycle Disorders Overview. GeneReviews. April 9, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1217/.
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.
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.
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.
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/.
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.