Disease Description (Causes and Symptoms)
- Cause/pathophysiology: This condition is inherited in an autosomal recessive manner and is caused by variants in the SLC25A13 gene. This gene encodes the aspartate–glutamate carrier (citrin), which functions in the mitochondria of the liver, kidneys, and other organs. Impaired citrin function disrupts the supply of aspartate to the urea cycle and the exchange of NADH/NAD+ between cells, resulting in abnormalities in ammonia removal and carbohydrate metabolism.
- Main phenotypes: The same genetic abnormality can present with different clinical features depending on age.
- CTLN2 (adult-onset citrullinemia type II): Usually manifests between 20 and 50 years of age (possible age of onset: 11–79 years). It is characterized by neuropsychiatric symptoms caused by hyperammonemia (including delirium, irritability/aggression, lethargy, disorientation, decreased memory, tremors, seizures, coma, and hepatic encephalopathy) and behavioral changes. Patients commonly show dietary preferences characterized by disliking sweet foods and carbohydrates and preferring protein and fat (carbohydrate avoidance). Alcohol, certain medications, surgery, and other factors may trigger episodic exacerbations. Some patients may develop pancreatitis, hyperlipidemia, and liver cancer (prevalence has been reported in some studies).
- NICCD (neonatal intrahepatic cholestasis caused by citrin deficiency): In infants younger than 1 year, cholestatic hepatitis, fatty liver, liver fibrosis, low weight and growth retardation, hypoproteinemia and coagulation disorders, hemolytic anemia, and hypoglycemia may occur; in many cases, these improve around 1 year of age.
- Diagnostic clues: Elevated blood ammonia, increased citrulline and arginine in plasma amino acids, and changes in the threonine/serine ratio may be observed. Definitive diagnosis is confirmed by molecular genetic testing of SLC25A13.
Treatment Methods and Precautions
- Acute hyperammonemia (emergency): Immediate medical emergency treatment should be provided (ammonia-lowering therapy—including nitrogen-scavenging medications and arginine supplementation, and hemodialysis if necessary).
- Chronic and baseline treatment
- CTLN2: Liver transplantation is considered the definitive treatment. For symptom control, oral arginine supplementation and a high-protein, high-fat, low-carbohydrate diet (with restriction of simple sugars) are recommended. Comorbidities such as hyperlipidemia and pancreatitis require individualized management.
- NICCD: Many cases improve with conservative treatment; when necessary, management may include supplementation with fat-soluble vitamins, lactose-free formula or special formula containing medium-chain triglycerides (MCT), and a high-protein, high-fat, low-carbohydrate diet.
- Medication and lifestyle precautions
- Be cautious about alcohol and certain medications known to trigger attacks (reported examples include acetaminophen [an antipyretic and analgesic] and proton pump inhibitors; anti-inflammatory and analgesic medications may also be included), as well as major surgery and fasting. Consult the treating physician before taking any medication.
- Regular monitoring of liver and pancreatic function and cancer development (hepatocellular carcinoma) is recommended, according to the physician’s judgment.
- Prognosis: NICCD improves after infancy in many cases. CTLN2 can cause severe neurological damage and fatal complications due to hyperammonemia, and may improve with liver transplantation.
Checkpoints Before an Outpatient Visit (Items to Prepare and Example Questions)
- Items to bring (recommended)
- A list of currently used medications and supplements (including dosage and duration of use)
- Previous test results (recent blood tests: liver function, ammonia, plasma amino acids, lipid tests, etc.) and genetic test results, if available
- Records of symptoms (seizures, decreased consciousness, abdominal pain, changes in appetite, etc.), dietary preferences (preferred and disliked foods), and recent history of alcohol use, surgery, or medication exposure
- For children, growth charts, formula details, and feeding records
- Information to tell the healthcare professional first during the outpatient visit
- Whether there have been recent changes in consciousness or seizures, and any recent situations that may have triggered acute worsening (alcohol use, medications, surgery, etc.)
- Family history (suspected cases of liver disease or genetic disease)
- Examples of brief questions patients can ask the doctor during the consultation
- “My ammonia level was high on a recent test. Do I need immediate treatment?”
- “Are there any foods that I must avoid in my diet?”
Examples of General Questions to Ask the Doctor
- “What are the expected effects and possible side effects of this medication (such as arginine)?”
- “What is my (or my child’s) long-term prognosis? When would liver transplantation be necessary?”
- “What medications, foods, or activities should I avoid in daily life? What should I do in an emergency?”
Examples of Disease-Specific Questions
- “If the SLC25A13 genetic test is positive, do you recommend testing family members (siblings and children)? What genetic counseling would you recommend?”
- “In adult-onset CTLN2, if symptoms cannot be controlled with conservative treatment before liver transplantation, what are the indications for liver transplantation and what is the prognosis?”
(If needed, I can also organize additional information about diagnostic testing methods, detailed emergency treatment, and the genetic testing process.)