Citrullinemia type II

Title

Other Names:

Citrullinemia type 2; Adult-onset citrullinemia type 2; CTLN2; Citrullinemia type 2; Adult-onset citrullinemia type 2; CTLN2; Citrin deficiency; Adult-onset citrullinemia type II; Adult-onset citrin deficiency; Adult-onset type II citrullinemia, See More

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Metabolic disorders; Congenital and Genetic Diseases; Digestive Diseases; Metabolic disorders; Newborn Screening See More

This disease is grouped under:

Urea cycle disorders

Summary Summary

Adult-onset citrullinemia type II is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. The condition chiefly affects the nervous system, causing confusion, restlessness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. These signs and symptoms can be life-threatening. The signs and symptoms appear during adulthood and are triggered by certain medications, infections, surgery, and alcohol intake. The features of adult-onset type II citrullinemia may also develop in people who as infants had a liver disorder called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). In many cases, the signs and symptoms of NICCD resolve within a year. Years or even decades later, however, some of these people develop the characteristic features of adult-onset type II citrullinemia. Adult-onset citrullinemia type II is caused by mutations in the SLC25A13 gene. This condition is inherited in an autosomal recessive pattern.^[1]

Last updated: 7/11/2011

Symptoms Symptoms

Adult-onset citrullinemia type II chiefly affects the nervous system, causing neuropsychiatric symptoms including nocturnal delirium, aggression, irritability, hyperactivity, delusions, disorientation, restlessness, drowsiness, loss of memory, flapping tremor, convulsive seizures, and coma. These signs and symptoms can be life-threatening. The signs and symptoms of this disorder appear suddenly during adulthood, usually between ages 20 and 50 years. The symptoms appear to be triggered by certain medications, infections, surgery, and alcohol intake.^[1]^[2] Many individuals with adult-onset citrullinemia type II are fond of protein-rich and/or fatty foods and have an aversion to carbohydrate-rich foods. Pathologic findings include fatty infiltration and mild fibrosis of the liver despite little or no liver dysfunction.^[2]

The features of adult-onset type II citrullinemia may also develop in people who as infants had a liver disorder called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). In many cases, the signs and symptoms of NICCD resolve within a year. Years or even decades later, however, some of these people develop the characteristic features of adult-onset type II citrullinemia.^[1]^[2]

Last updated: 7/11/2011

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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Acute hyperammonemia		0008281
Decreased body mass index		0045082
Elevated plasma citrulline		0011966
Hepatic steatosis	Fatty infiltration of liver Fatty liver [ more ]	0001397
30%-79% of people have these symptoms
Abnormal eating behavior		0100738
Aggressive behavior	Aggression Aggressive behaviour Aggressiveness [ more ]	0000718
Asterixis		0012164
Delirium		0031258
Delusions		0000746
Drowsiness	Sleepy	0002329
Elevated hepatic transaminase	High liver enzymes	0002910
Fluctuations in consciousness		0007159
Hallucinations	Hallucination Sensory hallucination [ more ]	0000738
Hepatomegaly	Enlarged liver	0002240
Hypertriglyceridemia	Increased plasma triglycerides Increased serum triglycerides Increased triglycerides [ more ]	0002155
Hypoalbuminemia	Low blood albumin	0003073
Hypoproteinemia	Decreased protein levels in blood	0003075
Irritability	Irritable	0000737
Lethargy		0001254
Memory impairment	Forgetfulness Memory loss Memory problems Poor memory [ more ]	0002354
Night sweats		0030166
Restlessness		0000711
Seizure		0001250
Sleep terror		0030765
Tremor		0001337
5%-29% of people have these symptoms
Cerebral edema	Swelling of brain	0002181
Coma		0001259
Decreased HDL cholesterol concentration	Decreased circulating high-density lipoprotein cholesterol Decreased HDL cholesterol Low HDL-cholesterol [ more ]	0003233
Delayed menarche	Delayed start of first period	0012569
Diarrhea	Watery stool	0002014
Echolalia	Echoing another person's speech	0010529
Enuresis		0000805
Global developmental delay		0001263
Hepatic encephalopathy		0002480
Hepatic fibrosis		0001395
Hepatocellular carcinoma		0001402
Hyperactivity	More active than typical	0000752
Hypercholesterolemia	Elevated serum cholesterol Elevated total cholesterol Increased total cholesterol [ more ]	0003124
Insomnia	Difficulty staying or falling asleep	0100785
Mania	Manic	0100754
Pancreatitis	Pancreatic inflammation	0001733
Psychosis		0000709
Vomiting	Throwing up	0002013
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Confusion	Disorientation Easily confused Mental disorientation [ more ]	0001289
Hyperammonemia	High blood ammonia levels	0001987

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

Last updated: 9/1/2020

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

Diagnosis 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.
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 Treatment

Liver transplantation for adult-onset citrullinemia type II prevents hyperammonemic crises, corrects metabolic disturbances, and eliminates preferences for protein-rich foods. Administration of arginine decreases blood ammonia concentration. Reduction in calorie and/or carbohydrate intake can lessen high triglycerides. Individuals with adult-onset citrullinemia type II are encouraged to consume a diet rich in lipids and protein and low in carbohydrates. This may help to prevent hyperammonemia.^[2]

Additional information related to the treatment of adult-onset citrullinemia type II can be accessed through eMedicine.

Last updated: 7/11/2011

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.

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

Prognosis Prognosis

The prognosis for individuals with adult-onset citrullinemia type ll varies. In babies, the signs and symptoms usually resolve on their own. In adults, treatment may reduce the signs and symptoms of the condition. As adult-onset citrullinemia type ll can cause severe liver problems, untreated adults may need a liver transplant.^[2]^[3]

Last updated: 12/28/2016

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.

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.

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: http://rarediseasesnetwork.epi.usf.edu/ucdc/takeaction/index.htm

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
Save Babies Through Screening Foundation, Inc
P.O. Box 2313
Palm Harbor, FL 34682-2313
Toll-free: 888-454-3383
E-mail: email@savebabies.org
Website: http://www.savebabies.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.

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 Citrullinemia type II. 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.

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 Citrullinemia type II. Click on the link to view a sample search on this topic.

News & Events News & Events

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Other Conferences

Reaching for a Cure: 2011 NUCDF Annual Conference, July 8 2011 - July 10, 2011
Location: Sheraton Denver Downtown, Denver, Colorado
Description: This conference offers the unique opportunity to meet other UCD families, stay informed, and learn about new advances in research, treatment and management to improve the lives of children and adults with UCD. Working together, our NUCDF families and community of committed researchers and medical professionals are making a major impact with advances in the understanding of UCDs, accelerating research, and improved outcomes in children and adults with UCD. In the past four years, research for UCDs has increased by 400%! Let's continue the momentum and end the devastating effects of UCD.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I have a patient with urine citrulline levels at twice the upper limit of normal. All other urinary amino acids were low-normal. This patient has legitimate complaints of decreased energy as well. Standard CPE labs were normal. What is the typical presentation of citrullinemia type II? How is it diagnosed? How is it treated? Who is conducting research into this condition. See answer
Why is adult onset citrullinemia type ll so common in Japan? What is the prognosis for this type of citrullinemia? Where can I find graphical data on the prevalence of citrullinemia worldwide? See answer

Have a question? Contact a GARD Information Specialist.