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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


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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


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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.

Showing of 46 |
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
Showing of 46 |
Do you have more information about symptoms of this disease? We want to hear from you.
Last updated: 2/1/2021
Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis


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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


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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


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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


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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 MedlinePlus Genetics.

Research Research


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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


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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


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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


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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 Citrullinemia type II. This website is maintained by the National Library of Medicine.

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


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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.

References References


  1. Citrullinemia. Genetics Home Reference (GHR). 2017; https://ghr.nlm.nih.gov/condition/citrullinemia.
  2. Kobayashi K, Saheki T. Citrin Deficiency. GeneReviews. July 31, 2014; http://www.ncbi.nlm.nih.gov/books/NBK1181/.
  3. Citrullinemia, Type II. baby's first test. http://www.babysfirsttest.org/newborn-screening/conditions/citrullinemia-type-ii. Accessed 12/28/2016.
Do you know of a review article? We want to hear from you.
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rare disease research!
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