Citrullinemia type II is a rare inherited disease in which the liver cannot use a substance called citrin properly, so ammonia and some amino acids build up in the blood. This problem happens because of harmful changes (mutations) in a gene called SLC25A13, which gives the body the plan to make the citrin protein. Citrin normally helps move small molecules in and out of the mitochondria in liver cells and supports the urea cycle, which safely removes extra nitrogen as urea. When citrin does not work, the urea cycle is disturbed, and this can cause high ammonia, confusion, and other serious brain and liver problems, especially in teenagers and adults.
Citrullinemia type II (also called adult-onset type II citrullinemia, CTLN2) is a genetic liver-metabolism disease where the body cannot remove ammonia well, so ammonia can build up in the blood and affect the brain. It happens because changes (mutations) in the SLC25A13 gene reduce a liver protein called citrin, which normally helps move key molecules in and out of mitochondria and supports energy handling in the liver. When citrin does not work well, the liver’s normal “ammonia-removal pathway” (urea cycle support) becomes unstable, and people can get episodes of confusion, strange behavior, sleepiness, seizures, or coma, often triggered by stressors like illness, alcohol, surgery, or some medicines.
Citrullinemia type II is part of a wider condition called citrin deficiency. Citrin deficiency can show different faces at different ages: liver disease in babies, poor growth and abnormal blood fats in children, and sudden brain and behavior problems with high ammonia in adolescents and adults (this adult form was traditionally called citrullinemia type II).
In most people, symptoms of citrullinemia type II appear between about 20 and 50 years of age. They often come as repeated attacks of confusion, strange behavior, or coma, usually when ammonia in the blood rises suddenly. Many reported patients are from East Asian countries, but cases are now found around the world.
Another names
Doctors and researchers use several other names for citrullinemia type II. All these names point to the same basic problem (citrin deficiency) but highlight different features or age groups:
Citrin deficiency – the broad name for the whole disease group caused by SLC25A13 mutations.
Adult-onset type II citrullinemia (CTLN2) – the classic name for the adolescent/adult brain form.
Adolescent and adult citrin deficiency (AACD) – newer name used instead of CTLN2 in many recent papers.
Citrullinemia, type II – often used in genetic and metabolic disease databases.
Citrullinemia type II / citrin deficiency (CIT II) – name used on newborn-screening and patient fact sheets.
SLC25A13-related citrullinemia type II – name that reminds us the disease is due to SLC25A13 gene changes.
Urea cycle disorder due to citrin deficiency – name that stresses the problem in the urea cycle.
Types
Citrullinemia type II sits inside the larger spectrum of citrin deficiency. The same gene defect can show up in different ways at different ages. Doctors usually describe three main, age-linked phenotypes (types):
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD)
This type appears in newborns and young babies. The baby may have long-lasting jaundice (yellow eyes and skin), poor feeding, poor weight gain, and liver problems. Blood tests show abnormal liver enzymes and high levels of some amino acids and other substances. Many babies get better with proper diet and care in the first years of life, but they still carry the gene change.Failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD)
This type appears in older infants and children. Children may be small for their age, tire easily, have fatty liver and abnormal blood fats, and complain of belly pain. They often strongly like high-protein, high-fat food and dislike sweet or starchy food such as rice and bread.Adolescent and adult citrin deficiency / classic citrullinemia type II (AACD / CTLN2)
This is the classic “citrullinemia type II” form. Teenagers or adults, often previously fairly well, suddenly develop high ammonia in the blood with confusion, strange behavior, sleepiness, seizures, or coma. Blood tests show high citrulline and other amino acids, and many people have fatty liver or other liver problems.
Some people with SLC25A13 mutations may stay almost symptom-free for years and are found only after tests for abnormal liver function or during family screening.
Causes
In simple words, there is one true basic cause and many triggers or risk factors that can bring on or worsen attacks.
Main genetic cause
SLC25A13 gene mutation (main cause)
The root cause is a harmful change (mutation) in both copies of the SLC25A13 gene. This gene gives instructions to make citrin, a transport protein in the inner membrane of mitochondria in liver cells. When citrin is missing or weak, many energy pathways in the liver do not work well, including the urea cycle. Ammonia and citrulline then build up in the blood, which can damage the brain and other organs.Autosomal recessive inheritance from carrier parents
Citrullinemia type II is passed on in an autosomal recessive pattern. This means a child must receive one non-working SLC25A13 gene from each parent to get the disease. Parents who carry only one changed gene are usually healthy but can pass the gene to their children. When both parents are carriers, each pregnancy has a 25% chance of having an affected child.Higher carrier frequency in some ethnic groups (especially East Asia)
Studies show SLC25A13 mutations are more common in people from Japan, China, Korea, Taiwan, and some Southeast Asian countries than in many Western countries. Because there are more carriers in these populations, citrullinemia type II is also more frequent there, though it can occur in any ethnic group.Parental consanguinity (parents related by blood)
When parents are related (for example, cousins), they are more likely to carry the same gene change. This increases the chance that a child will inherit two non-working copies of SLC25A13 and develop citrullinemia type II. This is a general feature of autosomal recessive diseases.
Triggers that can bring on or worsen attacks
These are not independent causes of the disease, but they raise stress on the liver and can bring out acute symptoms in someone who already has SLC25A13 mutations.
High-carbohydrate diet (too much sugar and starch)
In citrin deficiency, a high-carbohydrate diet is especially harmful. Extra sugar increases a chemical called NADH in the liver, which further blocks normal energy and urea cycle pathways. This can trigger hyperammonemia and brain symptoms, even though high-carbohydrate diets are usually used to help other urea cycle disorders.Intravenous high-glucose solutions and glycerol-rich fluids
Giving large amounts of glucose or glycerol through a vein (for example, in intensive care or after surgery) can sharply raise cytosolic NADH and make citrullinemia type II worse. There are reports of serious brain crises and even death after such infusions in people with citrin deficiency.Alcohol intake
Alcohol also increases NADH in the liver and can disturb many metabolic pathways. In patients with adult citrullinemia type II, alcohol drinking has been linked to sudden attacks of confusion and high ammonia levels.Acute infections (fever, sepsis, severe illness)
Severe infections raise the body’s energy demand and break down muscle protein, which increases ammonia production. In a person with citrullinemia type II, this extra load can push the urea cycle beyond its limit and trigger an attack of hyperammonemic encephalopathy.Major surgery or trauma
Operations and serious injuries stress the body, change eating patterns, and often require intravenous fluids high in glucose. Together, these factors increase metabolic stress in the liver and can bring on symptoms in citrin-deficient patients, especially if diet and fluids are not adjusted.Prolonged fasting or poor oral intake
When a person does not eat for a long time, the body breaks down its own proteins for energy. This produces more ammonia. In citrullinemia type II, the liver cannot handle this extra ammonia well, so fasting can trigger or worsen attacks.Use of medicines that raise ammonia (for example, valproate)
Some medicines, such as valproate (a seizure drug), are known to cause or worsen hyperammonemia and can unmask hidden urea-cycle problems. In people with citrin deficiency, these drugs may lead to dangerous increases in ammonia and confusion.Standard “low-protein / high-carbohydrate” treatment for hyperammonemia
In many urea-cycle disorders, doctors use a low-protein, high-calorie (often high-carbohydrate) diet to lower ammonia. But in citrullinemia type II, this standard approach actually makes things worse and can provoke or prolong brain symptoms.Non-alcoholic fatty liver disease linked to citrin deficiency
Citrin deficiency can cause fatty liver and sometimes liver scarring. Fatty liver and liver inflammation reduce the liver’s ability to handle ammonia and other toxins, making attacks more likely.Pregnancy and childbirth (in women with citrin deficiency)
Pregnancy changes metabolism and hormone levels, and delivery is a major physical stress. In people with underlying citrin deficiency, this extra load can trigger hyperammonemia and neuropsychiatric symptoms if diet and medical care are not carefully managed. (This is reported for urea-cycle disorders in general and also in case reports of citrin deficiency.)Very rapid weight loss or extreme dieting
Crash diets or very low-calorie regimens force the body to break down much more protein and fat. In citrullinemia type II, this extra nitrogen and metabolic stress can push the already weak urea cycle to failure, leading to elevated ammonia.Long-term under-recognised fatty liver disease in citrin deficiency
Some adults with citrin deficiency are first labeled as having “lean non-alcoholic fatty liver disease.” If the underlying citrin deficiency is not found, they may continue to receive standard high-carbohydrate advice, which increases the risk of later hyperammonemic crises.Misdiagnosis and inappropriate psychiatric treatment
Some patients with adult citrullinemia type II are first treated for psychiatric illnesses such as schizophrenia or mood disorders. If they receive drugs that affect the liver or appetite, or are given high-carbohydrate feeding, the underlying metabolic problem can worsen, leading to more severe attacks.Total parenteral nutrition with standard formulas
Total parenteral nutrition (TPN) often contains high glucose and sometimes glycerol. In citrin-deficient patients, standard TPN can strongly worsen metabolic stress and should be modified to avoid high carbohydrate. When standard TPN is used, it has been linked with severe hyperammonemia in such patients.Lack of early diagnosis and dietary education
If citrin deficiency is not recognized, patients may be advised to eat the opposite of what they need (for example, more sweets and less protein). Over many years this mismatch increases the risk of fatty liver, energy failure, and sudden hyperammonemia in adulthood.Other liver diseases on top of citrin deficiency
If a person with SLC25A13 mutations also develops another liver disease (for example, viral hepatitis, alcoholic liver disease, or other chronic liver damage), the combined effect further lowers liver reserve and makes attacks of citrullinemia type II more likely and more dangerous.
Symptoms
Not every patient has every symptom, and the pattern can change from attack to attack. But common symptoms in adolescents and adults with citrullinemia type II include:
Confusion and disorientation
The person may seem “out of it,” not know where they are or what day it is, or give strange answers. This happens because high ammonia and other toxins affect brain cells and change how they work.Abnormal behavior or personality change
Families often notice sudden aggression, irritability, strange actions, or psychiatric-like symptoms (for example, hallucinations or severe anxiety). These changes are due to brain dysfunction from hyperammonemia, not just a primary mental illness.Excessive sleepiness or reduced alertness
The person may sleep much more than usual, be hard to wake, or seem “drowsy all the time.” As ammonia rises further, this can progress to stupor and coma if not treated.Seizures (fits)
Some patients have seizures during severe attacks. Seizures occur because toxic effects of high ammonia disturb the normal electrical activity of the brain.Headache
Headaches, sometimes severe, are common and may be a sign of brain swelling or high intracranial pressure during hyperammonemia.Nausea and vomiting
Many people with an acute attack feel sick to their stomach and may vomit repeatedly. This is a common non-specific sign of high ammonia and brain irritation.Poor appetite and food refusal
People often lose appetite, especially for sweet or starchy foods. Long term, many patients prefer high-protein, high-fat foods such as meat, eggs, cheese, and nuts and dislike rice, bread, and sweets, which is a hallmark of citrin deficiency.Weight loss and low body mass index (BMI)
Because patients avoid many carbohydrate foods and may have repeated illness, they often lose weight and have a low BMI, even while having fatty liver.Fatty liver and liver enzyme abnormalities
Blood tests often show raised liver enzymes, and imaging may show fat in the liver. Some patients develop more serious liver disease or even liver cancer at a relatively young age if the problem is not managed.Abdominal pain and discomfort
Many patients complain of belly pain, bloating, or discomfort, especially after eating the “wrong” foods that are high in sugar or starch.Tiredness and low energy
Even between attacks, people may feel easily tired. The liver cannot make energy efficiently because key metabolic pathways are disturbed, so the whole body can feel weak.Sleep problems at night (for example, night-time delirium)
Some patients have strange dreams, talk or shout at night, or seem confused mainly during the night. These night-time changes in behavior are typical in some cases of adult citrullinemia type II.Breathing changes and respiratory alkalosis
In severe hyperammonemia, people may breathe fast and deep. Blood tests show low carbon dioxide (respiratory alkalosis). This change is part of the body’s response to metabolic stress.Coma in severe attacks
Without quick treatment, confusion and sleepiness can progress to coma. In this state the person does not respond to voice or pain and needs intensive care. This is a life-threatening emergency.Long-term cognitive or psychiatric problems if repeated attacks occur
Repeated episodes of high ammonia can cause lasting damage to the brain. Some patients later show ongoing learning problems, slower thinking, memory difficulties, or chronic psychiatric symptoms, even after the acute attacks are controlled.
Diagnostic tests
Doctors use a mix of clinical examination and laboratory / imaging tests to diagnose citrullinemia type II and to see how severe it is. Below, tests are grouped into physical exam, manual (bedside) tests, lab and pathological tests, electrodiagnostic tests, and imaging tests.
Physical exam tests
General physical examination
The doctor looks at overall appearance: level of alertness, signs of confusion, body weight, and signs of long-term illness such as muscle wasting. They also check for tremors, abnormal movements, and signs of liver disease such as jaundice or enlarged liver. These clues help suspect a metabolic or liver-based cause for the symptoms rather than a purely psychiatric problem.Liver-focused abdominal examination
The doctor feels (palpates) the abdomen to see if the liver is enlarged or tender and checks for fluid in the abdomen (ascites). In citrin deficiency–related disease, fatty liver and other structural changes are common, so this exam often shows a slightly enlarged, sometimes fatty liver.Neurological examination
The doctor checks reflexes, muscle strength, muscle tone, coordination, and balance. In hyperammonemic encephalopathy, they may find brisk reflexes, flapping tremor of the hands (asterixis), or poor coordination. These findings show the brain is affected by toxins such as ammonia.Mental status examination
The clinician asks simple questions about time, place, person, and memory, such as “What is your name?” or “What day is it today?” In citrullinemia type II, patients may give wrong answers, speak slowly, or show poor attention, which fits with metabolic encephalopathy rather than a primary mental health disorder.
Manual (bedside) tests
Hand-grip strength and simple muscle tests
The doctor asks the patient to squeeze their hand or push and pull against resistance. These simple tests help check for general weakness, which can be present in metabolic disorders with high ammonia. They are easy to repeat and help follow improvement as ammonia levels fall.Coordination tests (for example, finger-to-nose test)
The person is asked to touch their nose and then the doctor’s finger repeatedly. In encephalopathy, movements may become slow, shaky, or inaccurate. This supports the idea that the brain is being affected by toxins from the liver.Gait observation (watching how the person walks)
The doctor asks the person to walk a few steps, turn, and come back. People with significant brain involvement may walk unsteadily, have a wide-based gait, or need help to stand. Changes in gait in the setting of high ammonia suggest metabolic encephalopathy.Simple cognitive tasks (for example, serial sevens, drawing a clock)
The clinician may ask the person to subtract seven repeatedly from 100, or to draw a clock face. Difficulty performing these tasks, especially when combined with abnormal labs, supports a diagnosis of brain involvement from metabolic disease like citrullinemia type II.
Lab and pathological tests
Plasma ammonia level
This is one of the most important tests. In citrullinemia type II, plasma ammonia is usually elevated during attacks, sometimes very high. High ammonia confirms a urea-cycle-related problem and explains the brain symptoms.Plasma amino acid profile (especially citrulline)
Blood is tested for many amino acids using special machines (tandem mass spectrometry). In citrin deficiency / citrullinemia type II, citrulline and some other amino acids (such as threonine, tyrosine, and methionine) are often elevated. This pattern helps distinguish it from other urea cycle disorders.Newborn screening amino acid panel (where available)
In some places, newborn screening programs can detect citrin deficiency by finding abnormal levels of certain amino acids shortly after birth. If a baby tests positive, further tests confirm the diagnosis and allow early diet changes that may prevent severe later problems, including adult citrullinemia type II.Liver function tests (ALT, AST, GGT, bilirubin, albumin)
These common blood tests measure liver cell damage and bile flow. Many patients with citrullinemia type II have raised ALT and AST, sometimes raised GGT, and changes in bilirubin. Low albumin and clotting problems may appear if liver function is poor. The pattern can help suspect citrin deficiency and rule out other liver diseases.Serum lipid profile (cholesterol and triglycerides)
Children and adults with citrin deficiency often have abnormal blood fats, especially high triglycerides. This test helps identify the FTTDCD stage and shows how the liver is handling fat.Blood glucose and lactate / pyruvate tests
Some patients have low blood sugar (hypoglycemia) and abnormal lactate / pyruvate ratios, showing energy problems in the liver. These results support a diagnosis of citrin deficiency rather than a simple psychiatric illness or isolated liver problem.Urine organic acids and orotic acid
Urine can be tested for organic acids and orotic acid to help distinguish citrullinemia type II from other urea-cycle defects. In citrin deficiency, the pattern of these substances differs from classic citrullinemia type I or other enzyme deficiencies.Genetic testing for SLC25A13 mutations
Finding disease-causing mutations in the SLC25A13 gene is the gold-standard way to confirm citrullinemia type II. Genetic testing can also identify carriers and help with family counseling and screening of siblings or other relatives.Special markers such as pancreatic secretory trypsin inhibitor (PSTI)
Some studies have shown high blood levels of PSTI in patients with adult citrullinemia type II, which may drop after successful liver transplantation. While not used everywhere, this marker can support the diagnosis in expert centers.Liver biopsy (histology)
In unclear cases, a small piece of liver may be taken for microscopic study. In citrin deficiency, the biopsy often shows fatty change, abnormal glycogen, and other typical patterns. However, because biopsy is invasive, doctors now often prefer genetic testing and detailed imaging instead.
Electrodiagnostic tests
Electroencephalogram (EEG)
EEG records the brain’s electrical activity. In adult-onset citrullinemia type II, EEG usually shows diffuse slowing of brain waves during attacks, which is typical of metabolic encephalopathy. EEG findings often improve as ammonia levels fall or after liver transplantation.Nerve and muscle conduction / evoked potential studies (in selected cases)
These tests check how fast nerves and muscles respond to electrical signals or sensory input. They may be done if there is concern about other neurological diseases. In citrullinemia type II, they are usually normal or show non-specific changes, helping rule out other causes of weakness or seizures.
Non-Pharmacological Treatments (therapies + other steps)
1) Low-carbohydrate, higher-protein, higher-fat meal pattern (main diet therapy).
Purpose: reduce “carb overload” stress on the liver and lower risk of ammonia spikes. Mechanism: citrin deficiency impairs liver carbohydrate handling; lowering carbs and using more fat/protein can match how many patients tolerate food better and may reduce attack triggers.
2) Avoid alcohol completely.
Purpose: prevent sudden ammonia crises and brain symptoms. Mechanism: alcohol stresses the liver and can trigger hyperammonemia/encephalopathy episodes in CTLN2.
3) Medium-chain triglyceride (MCT) oil or MCT-based formulas (diet add-on).
Purpose: provide “easier” energy and support nutrition when carbs are limited. Mechanism: MCTs are absorbed and used differently than long-chain fats and may help energy balance; reports and reviews describe benefit and prevention support in citrin deficiency/CTLN2 context.
4) Eat regularly; avoid prolonged fasting.
Purpose: reduce catabolic stress (body breaking down its own protein), which can raise ammonia. Mechanism: stable calorie intake reduces muscle breakdown and nitrogen load during stress.
5) Emergency “sick-day” plan (written steps).
Purpose: act early during fever, vomiting, infection, or poor intake. Mechanism: early hospital evaluation and ammonia-lowering steps can prevent brain injury from severe hyperammonemia.
6) Rapid treatment of infections (early doctor contact).
Purpose: avoid metabolic crashes triggered by illness. Mechanism: infections increase stress hormones and catabolism, which can push ammonia up.
7) Avoid very high-sugar drinks and very high-carb meals (especially “binge” carbs).
Purpose: reduce attack triggers. Mechanism: CTLN2 is linked with impaired hepatic carbohydrate handling; large carb loads can worsen symptoms for some patients.
8) Work with a metabolic dietitian (specialist nutrition care).
Purpose: customize protein/fat/carb targets safely and prevent deficiencies. Mechanism: individual tolerance varies; expert diet planning helps maintain growth/weight while lowering ammonia risk.
9) Avoid “wrong” standard hepatic-encephalopathy diet advice unless your specialist approves.
Purpose: prevent harmful over-restriction or wrong macro balance. Mechanism: CTLN2 dietary needs can differ from typical liver failure advice; specialist guidance matters.
10) Avoid glycerol infusions unless a specialist says it is safe.
Purpose: reduce risk of worsening brain symptoms in CTLN2. Mechanism: GeneReviews notes reports of worsened encephalopathy after IV glycerol therapy in CTLN2.
11) Manage sleep and prevent sleep deprivation.
Purpose: reduce stress and help detect early mental changes. Mechanism: poor sleep can worsen confusion and may hide early encephalopathy signs; stable sleep supports safer monitoring.
12) Avoid extreme exercise during illness or poor intake.
Purpose: prevent protein breakdown and ammonia rise. Mechanism: over-exertion during low calorie intake increases catabolism and nitrogen load.
13) Gentle, consistent activity (when stable).
Purpose: support metabolic health and fatty liver risk reduction. Mechanism: stable activity supports insulin sensitivity and liver fat balance; CTLN2 can be linked with fatty liver/metabolic issues.
14) Avoid dehydration; maintain fluids.
Purpose: reduce stress on the body and improve stability. Mechanism: dehydration worsens illness stress and can make nausea/vomiting harder to manage, increasing crisis risk.
15) Medical ID bracelet/card (“Citrin deficiency / risk of hyperammonemia”).
Purpose: faster correct emergency treatment. Mechanism: alerts ER teams to check ammonia early and consider urea-cycle emergency protocols.
16) Family screening and genetic counseling.
Purpose: identify carriers/affected relatives and plan early monitoring. Mechanism: CTLN2 is inherited (autosomal recessive) through SLC25A13 changes.
17) Avoid alcohol-related social “pressure” plans (practical prevention).
Purpose: reduce relapse triggers. Mechanism: alcohol is a known trigger; planning alternatives prevents exposure.
18) Pre-surgery planning with anesthesia + metabolic team.
Purpose: prevent peri-operative hyperammonemia. Mechanism: surgery stress can trigger episodes; planned monitoring and nutrition/drug strategy lowers risk.
19) Regular monitoring (labs + nutrition status) as your specialist advises.
Purpose: catch rising ammonia risk, liver stress, and nutrition gaps early. Mechanism: CTLN2 can be episodic; trend monitoring helps prevention.
20) Liver transplant evaluation early if episodes are severe or recurrent.
Purpose: long-term definitive control in severe CTLN2. Mechanism: replacing the liver can correct the major metabolic problem and prevent repeated hyperammonemic crises.
Drug Treatments
1) Sodium phenylacetate + sodium benzoate IV (AMMONUL) — emergency ammonia scavenger.
Drug class: nitrogen-scavenging agents. Dosage/time: IV regimen is weight-based in the FDA label; used urgently in hospital. Purpose: rapidly lower ammonia in severe hyperammonemia. Mechanism: provides alternative pathways to remove nitrogen as excretable compounds. Side effects: can include metabolic issues, electrolyte changes, and infusion risks; requires close monitoring.
2) Glycerol phenylbutyrate (RAVICTI) — chronic nitrogen scavenger.
Drug class: nitrogen-binding agent for chronic UCD management. Dosage/time: taken with food; dose is individualized and titrated by specialists. Purpose: help keep ammonia controlled long-term. Mechanism: metabolized to phenylacetate which binds nitrogen for removal. Side effects: GI symptoms and other label-listed effects; monitoring is required.
3) Sodium phenylbutyrate (BUPHENYL) — chronic nitrogen scavenger.
Drug class: nitrogen-scavenging agent. Dosage/time: FDA label describes usual total daily dosing ranges and divided dosing with meals/feeds. Purpose: long-term ammonia control in UCDs when diet alone is not enough. Mechanism: converts nitrogen waste into compounds that can be excreted. Side effects: GI upset, taste issues, and metabolic monitoring needs.
4) Lactulose — lowers ammonia by changing gut chemistry (supportive).
Drug class: osmotic laxative; used in hepatic encephalopathy care. Dosage/time: titrated to produce soft stools as directed by clinician. Purpose: reduce ammonia absorbed from the gut. Mechanism: acidifies colon contents and promotes ammonia trapping/excretion plus faster transit. Side effects: diarrhea, dehydration, electrolyte imbalance if overused.
5) Rifaximin (XIFAXAN) — gut-target antibiotic used to reduce ammonia-producing bacteria (supportive).
Drug class: rifamycin antibacterial. Dosage/time: label includes 550 mg twice daily for hepatic encephalopathy recurrence prevention in adults (not CTLN2-specific). Purpose: lower gut ammonia production as part of a specialist plan. Mechanism: reduces intestinal bacteria that make ammonia. Side effects: GI symptoms; rare allergy; watch drug interactions as advised.
6) Carglumic acid (CARBAGLU) — only for specific UCD pathways; sometimes used if diagnosis is uncertain in acute hyperammonemia.
Drug class: urea-cycle activator for NAGS deficiency. Dosage/time: FDA label gives 100–250 mg/kg/day for acute hyperammonemia in its indicated condition. Purpose: in the right diagnosis, it helps the urea cycle start working better. Mechanism: replaces an activator that turns on carbamoyl phosphate synthetase I. Side effects: GI symptoms are common; specialist monitoring needed.
7) Arginine hydrochloride injection (IV arginine) — nitrogen support in UCD emergency protocols (specialist-directed).
Drug class: amino acid therapy (support). Dosage/time: FDA label text for sodium phenylacetate/benzoate products discusses IV arginine use in suspected UCD hyperammonemia (pediatric protocol context). Purpose: support urea-cycle intermediates and nitrogen handling in some UCD settings. Mechanism: provides substrate that can help push nitrogen through safer pathways (condition-dependent). Side effects: acid–base and electrolyte issues can occur; needs monitoring.
8) Dextrose IV (when used for parenteral calories) — catabolism prevention in crisis (must be individualized for CTLN2).
Drug class: carbohydrate calorie source for IV nutrition. Dosage/time: depends on clinical setting; used in hospital. Purpose: reduce protein breakdown that can raise ammonia during stress. Mechanism: provides calories so the body breaks down less muscle protein. Side effects: hyperglycemia and fluid/electrolyte issues can occur; careful monitoring required.
9) Levetiracetam (KEPPRA / KEPPRA XR) — seizure control if seizures occur during episodes.
Drug class: antiepileptic. Dosage/time: individualized; follow neurology guidance. Purpose: stop or prevent seizures that can happen during hyperammonemia. Mechanism: stabilizes brain signaling (exact mechanism not fully defined in label). Side effects: sleepiness, dizziness, mood/behavior changes in some people.
10) Lorazepam injection (ATIVAN Injection) — emergency seizure stopping medicine in hospital.
Drug class: benzodiazepine. Dosage/time: emergency, clinician-administered. Purpose: stop active seizures quickly. Mechanism: increases GABA-A activity to calm abnormal brain firing. Side effects: breathing suppression and heavy sedation risk; needs monitoring.
11) Ondansetron (ZOFRAN) — nausea/vomiting control to protect intake during illness.
Drug class: 5-HT3 receptor antagonist antiemetic. Dosage/time: clinician-directed based on age/setting. Purpose: reduce vomiting so dehydration/fasting triggers are less likely. Mechanism: blocks serotonin signaling that triggers nausea/vomiting. Side effects: headache, constipation; QT-risk in some patients.
12) Sodium phenylacetate + sodium benzoate (newer labeled versions) — same emergency class as AMMONUL.
Drug class: nitrogen scavengers. Dosage/time: weight-based IV protocols per label. Purpose/mechanism: emergency nitrogen removal when ammonia is dangerous. Side effects: metabolic disturbances; infusion monitoring required.
13) Transition to oral scavengers after crisis (specialist step-down).
Drug class: oral nitrogen scavengers (phenylbutyrate/phenylbutyrate pro-drug). Dosage/time: started after ammonia is controlled. Purpose: prevent rebound hyperammonemia. Mechanism: continues nitrogen removal through alternative excretion. Side effects: varies by product; labs needed.
14) Enteral feeding support medicines (for tube administration of key therapies).
Drug class: administration strategy using labeled tube instructions (product-specific). Dosage/time: depends on medication and feeding tube type. Purpose: ensure reliable intake when swallowing is hard. Mechanism: maintains steady dosing and calories to reduce catabolic stress. Side effects: tube blockage/aspiration risks (caregiver training needed).
15) Specialist-prescribed oral arginine (not a cure; supportive for some patients).
Drug class: amino acid therapy. Dosage/time: individualized. Purpose: help lower ammonia risk in selected cases. Mechanism: supports urea-cycle intermediates depending on metabolic state. Side effects: GI upset; electrolyte/acid–base issues in some settings.
16) Rapid IV fluids/electrolyte correction (hospital supportive meds/solutions).
Drug class: IV fluids and electrolyte replacements. Dosage/time: clinician-directed. Purpose: stabilize circulation and prevent worsening brain effects. Mechanism: corrects dehydration/electrolyte imbalance that can worsen encephalopathy. Side effects: fluid overload risk; monitoring required.
17) Antibiotic strategy for gut ammonia reduction (when selected by clinicians).
Drug class: gut-acting antibiotic option (rifaximin-based). Dosage/time: per label for HE recurrence prevention (adults). Purpose: lower ammonia-producing bacteria load. Mechanism: local gut antibacterial action with low absorption. Side effects: GI symptoms; resistance considerations.
18) Laxative strategy for ammonia control (lactulose-based titration).
Drug class: osmotic laxative. Dosage/time: adjusted to stool goal under clinician direction. Purpose: reduce ammonia absorption. Mechanism: traps ammonia in colon and speeds removal. Side effects: diarrhea/dehydration if overtitrated.
19) Hospital rescue escalation if medicines are not fast enough (dialysis is a procedure, but paired with meds).
Drug class: “more rapid interventions” are needed in acute hyperammonemia; drug labels emphasize this. Purpose: prevent brain injury when ammonia is very high. Mechanism: rapid ammonia reduction plus ongoing scavenger therapy. Side effects: depends on procedure/ICU care.
20) Medication avoidance plan (important “drug treatment” = avoiding harmful triggers).
Drug class: prevention strategy. Purpose: reduce attacks triggered by medicines, alcohol, or stressors. Mechanism: known triggers can precipitate encephalopathy; a clinician-reviewed “avoid list” reduces risk.
Dietary Molecular Supplements
1) MCT oil (as a nutrition supplement).
Dosage: individualized (small amounts and titrate). Function: calorie support with low carb intake. Mechanism: MCTs are metabolized in a way that may support energy balance in citrin deficiency management plans.
2) Essential fatty acids (omega-3) — nutritional support.
Dosage: clinician-guided. Function: supports heart/lipid balance and inflammation control. Mechanism: may support triglyceride and liver-fat risk management, which can be relevant in citrin deficiency metabolic patterns.
3) L-arginine (as an oral medical nutrition supplement in some plans).
Dosage: individualized. Function: urea-cycle intermediate support. Mechanism: provides substrate that can support nitrogen handling in selected UCD management strategies.
4) Multivitamin with minerals (baseline nutrition protection).
Dosage: typical daily dose as advised. Function: prevents micronutrient gaps when diet is restricted. Mechanism: ensures vitamins/minerals remain adequate when carbs are limited and food choices are narrow.
5) Vitamin D (if low) — bone and immune support.
Dosage: based on blood level. Function: bone health. Mechanism: corrects deficiency risk in restricted diets and supports muscle and immune function.
6) Calcium (if intake is low).
Dosage: dietitian-guided. Function: bone strength. Mechanism: supports bone mineral needs if dairy/carbohydrate foods are reduced or avoided.
7) Magnesium (if low or cramps occur).
Dosage: clinician-guided. Function: muscle/nerve function. Mechanism: supports neuromuscular stability and helps correct deficiency from restricted diet or diarrhea from lactulose.
8) Zinc (if poor appetite or frequent infections).
Dosage: clinician-guided. Function: immune support and wound healing. Mechanism: supports enzyme function and immune response; deficiency can happen with limited diets.
9) Selenium (only if low; avoid excess).
Dosage: lab-guided. Function: antioxidant enzyme support. Mechanism: supports glutathione-related antioxidant defenses, helpful when liver stress is present.
10) Carnitine (only if deficiency/need is confirmed).
Dosage: clinician-guided. Function: supports fat transport into mitochondria. Mechanism: carnitine is required for long-chain fat oxidation; supplementation is sometimes used when secondary deficiency exists.
Drugs for immunity support / organ support
Important truth: There are no FDA-approved “stem cell drugs” that fix CTLN2, and “immune boosters” do not remove ammonia by themselves. The drugs below are supportive and may be used in certain situations by specialists to protect organs or correct deficiencies, but they do not replace core ammonia control and diet therapy.
1) Levocarnitine (CARNITOR) — metabolic support if secondary deficiency exists.
Dosage: individualized; oral or IV per clinician. Function: supports energy production, especially fat oxidation. Mechanism: helps transport long-chain fatty acids into mitochondria; used for inborn errors causing secondary carnitine deficiency.
2) N-acetylcysteine IV (ACETADOTE) — liver antioxidant support in selected liver-stress situations (off-label logic).
Dosage: clinician-directed (label is for acetaminophen overdose). Function: boosts glutathione pathways. Mechanism: replenishes antioxidant capacity and can protect liver cells in certain toxic/stress states (decision by doctors).
3) Phytonadione (Vitamin K1; AquaMEPHYTON/Mephyton) — bleeding-risk support if vitamin K is low.
Dosage: clinician-directed. Function: supports blood clotting factor activation. Mechanism: restores vitamin K–dependent clotting pathways if deficiency occurs with liver or nutrition problems.
4) Ursodiol (URSO / Actigall) — bile flow support if cholestasis/bile issues are present.
Dosage: clinician-directed. Function: improves bile acid flow in certain liver diseases. Mechanism: changes bile composition and can reduce toxic bile acids; used when doctors diagnose a bile-flow problem.
5) Ondansetron (ZOFRAN) — “intake protection” during vomiting illnesses.
Dosage: clinician-directed. Function: prevents vomiting and dehydration. Mechanism: blocks 5-HT3 receptors to reduce nausea/vomiting triggers, helping prevent fasting-related metabolic stress.
6) Dextrose IV (parenteral calorie support) — crisis support to reduce catabolism (careful use in CTLN2).
Dosage: clinician-directed. Function: provides calories quickly in hospital. Mechanism: reduces muscle breakdown and nitrogen release during severe illness; must be balanced with CTLN2-specific tolerance and monitoring.
Surgeries / Procedures (what they are, and why done)
1) Liver transplantation.
Procedure: replace diseased liver with a donor liver. Why done: severe/recurrent CTLN2 attacks can be life-threatening; transplant is considered the most definitive therapy reported for long-term prognosis in severe CTLN2.
2) Hemodialysis or continuous renal replacement therapy (CRRT) for hyperammonemia crisis (procedure).
Procedure: blood-filtering machine in ICU. Why done: if ammonia is dangerously high, procedures may be required because drug labels stress that acute hyperammonemia needs rapid interventions beyond slow medicines.
3) Central venous line placement (procedure).
Procedure: a large IV catheter placed in a big vein. Why done: allows safe infusion of emergency IV scavengers, glucose/fluids, and frequent blood tests during metabolic crisis care.
4) Feeding tube placement (NG tube or gastrostomy) when oral intake is unsafe.
Procedure: tube into stomach (temporary or long-term). Why done: ensures steady delivery of calories and medicines (some drug labels include tube-administration instructions), reducing fasting and missed dosing.
5) Intensive monitoring admission (ICU-level management as a “care procedure”).
Procedure: continuous monitoring and repeated ammonia checks. Why done: brain symptoms and seizures can happen fast; tight monitoring prevents complications while ammonia is being lowered.
Preventions (simple, practical)
1) Strict no-alcohol rule.
2) Keep carbs low; avoid sugar binges.
3) Use MCT support if your team recommends it.
4) Do not skip meals; avoid fasting.
5) Treat infections early; have a sick-day plan.
6) Wear a medical ID that mentions hyperammonemia risk.
7) Plan ahead for surgery/anesthesia with a metabolic team.
8) Avoid dehydration; maintain fluids during heat/illness.
9) Review medications with your doctor (avoid triggers).
10) Regular follow-up labs and diet review.
When to see doctors (and when it is an emergency)
See a metabolic specialist as soon as possible after diagnosis (or suspicion) to build a diet + medication plan and a written emergency plan, because CTLN2 can look like “mental changes” but is actually a dangerous ammonia problem.
Go to the emergency room immediately for sudden confusion, extreme sleepiness, repeated vomiting, unusual aggressive/abnormal behavior, new seizure, or trouble staying awake—these can be signs of hyperammonemic encephalopathy and need urgent ammonia testing and rapid treatment.
What to eat and what to avoid (simple food guide)
1) Eat: eggs, fish, chicken/meat (as advised) | Avoid: big bowls of rice/sugar drinks.
2) Eat: healthy fats (olive oil, nuts) | Avoid: candy, cakes, sweet juices.
3) Eat: MCT oil if prescribed | Avoid: alcohol (any amount).
4) Eat: small frequent meals | Avoid: fasting or “one meal a day.”
5) Eat: vegetables (non-starchy) | Avoid: very high-starch “carb loading.”
6) Eat: adequate fluids | Avoid: dehydration (especially during fever/diarrhea).
7) Eat: protein/fat pattern your dietitian sets | Avoid: copying liver-failure diets without specialist input.
8) Eat: planned snacks during travel/exams | Avoid: long gaps between meals.
9) Eat: balanced micronutrients (vitamins/minerals if needed) | Avoid: random megadose supplements.
10) Eat: what you tolerate best within the plan | Avoid: “trigger experiments” (alcohol/high-carb tests).
FAQs
1) Is citrullinemia type II the same as type I? No—type II is linked to citrin (SLC25A13) problems and often has different diet needs.
2) Why is ammonia dangerous? High ammonia can poison the brain and cause confusion, seizures, or coma.
3) What triggers attacks? Illness, alcohol, surgery, some medicines, and metabolic stress can trigger episodes.
4) What is the key diet idea? Many patients do better with low carbs and relatively higher protein/fat under specialist guidance.
5) Does everyone with citrin deficiency get adult CTLN2? No—only a portion develop adult-onset attacks.
6) Can CTLN2 look like a mental illness? Yes, because ammonia can cause behavior and memory changes.
7) What test confirms it? Doctors use blood amino acids, ammonia, and genetic testing of SLC25A13.
8) Is there a cure? The most definitive option in severe cases is liver transplantation.
9) Are ammonia-scavenger drugs “forever”? Sometimes long-term, but only if a specialist decides diet alone is not enough.
10) Can lactulose help? It can help lower ammonia from the gut in some care plans (doctor-guided).
11) Can rifaximin help? It can reduce gut ammonia production in hepatic encephalopathy care; specialists may consider it as support.
12) Should I take “immune boosters” to treat CTLN2? They do not remove ammonia; do not rely on them instead of real metabolic treatment.
13) Is exercise allowed? Yes when stable, but avoid extreme exertion during illness or fasting.
14) What is the most important emergency action? Go to the ER and ask for an ammonia level if severe confusion, vomiting, or seizures occur.
15) Can family members be carriers? Yes—this is inherited in an autosomal recessive pattern, so family testing may help.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 26, 2025.
