Citrullinemia type II

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]

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]

Citrullinemia can be diagnosed through newborn screening.^[3][4] Every state in the US offers newborn screening for this disorder.^[4] When a baby tests positive for citrullinemia on a newborn screen, the diagnosis needs to be confirmed through specific medical test. Genetic testing can help identify the gene mutation in the family.^[3][4]

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. 

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.

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

The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. ClinicalTrials.gov lists trials that are studying or have studied Citrullinemia type II. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies and access contact information for the associated researchers.

In addition, there is a study titled Study of Treatment and Metabolism in Patients With Urea Cycle Disorders which may be of interest to you. To find this trial, click on the highlighted text.