Citrin deficiency, a rare genetic disorder, causes repeated episodes of brain swelling and confusion from ammonia buildup in young adults, even when the liver appears healthy. According to Gram Research analysis of two confirmed cases, both patients carried the same genetic mutation in the SLC25A13 gene and experienced ammonia levels ranging from 103 to 345 micromoles per liter during symptomatic episodes. Treatment with ammonia-lowering medications and dietary changes emphasizing carbohydrates eliminated recurrent episodes in both patients over 6 months of follow-up.
Researchers discovered that a rare genetic condition called citrin deficiency can cause repeated episodes of brain swelling and confusion in young adults, even when the liver appears relatively healthy. According to Gram Research analysis, this condition occurs when the body cannot properly process certain nutrients, leading to dangerous ammonia buildup in the blood. Two young Vietnamese men with this disorder showed unusual food preferences, avoiding carbohydrates while craving protein and fat. When doctors identified the genetic cause and adjusted their diets while giving ammonia-lowering medication, both patients stopped having these dangerous episodes. This case report highlights that doctors should consider citrin deficiency when young adults have unexplained brain problems linked to ammonia.
Key Statistics
A 2026 case report of two genetically confirmed patients found that citrin deficiency caused ammonia levels to spike between 103 and 345 micromoles per liter during symptomatic episodes, despite relatively preserved liver function.
Both patients in a 2026 case report showed complete resolution of recurrent encephalopathic episodes within 6 months of starting ammonia-lowering therapy combined with a carbohydrate-enriched, protein and fat-restricted diet supplemented with medium-chain triglycerides.
A 2026 analysis of two citrin deficiency cases revealed that both patients harbored the identical homozygous SLC25A13 gene mutation and shared a lifelong preference for protein and fat-rich foods while avoiding carbohydrates, suggesting dietary patterns may reflect the underlying genetic disorder.
The Quick Take
- What they studied: Why two young men kept having episodes of confusion, behavioral problems, and brain swelling caused by ammonia buildup in their blood
- Who participated: Two unrelated young Vietnamese men, ages 18 and 21, who experienced repeated neuropsychiatric episodes over time
- Key finding: Both patients had the same rare genetic mutation that prevents their bodies from properly processing nutrients, causing ammonia to accumulate to dangerous levels (ranging from 103 to 345 micromoles per liter during episodes)
- What it means for you: If you or someone you know experiences repeated episodes of confusion, behavioral changes, or brain fog alongside unusual food cravings, doctors should test for this rare genetic condition. Early diagnosis and dietary management can prevent serious complications. However, this is an extremely rare disorder, so it would only apply to a tiny fraction of people with these symptoms.
The Research Details
This research presents two detailed case reports of individual patients with a rare genetic disorder. The doctors carefully documented each patient’s medical history, symptoms, blood test results, brain imaging, and genetic testing. They used whole-exome sequencing, a technology that reads nearly all of a person’s genes, to identify the specific genetic mutation causing the problem. The findings were then confirmed using Sanger sequencing, a more targeted genetic test that double-checks the results.
The researchers examined both patients’ dietary habits, brain function tests, and liver health to understand how the genetic mutation affected their bodies. They tracked how the patients responded to treatment with ammonia-lowering medications and dietary changes over a 6-month follow-up period.
This type of case report is valuable because it describes rare conditions that most doctors rarely encounter. By documenting these cases in detail, the researchers help other physicians recognize similar patients and provide appropriate treatment.
Case reports like this one are crucial for identifying rare diseases that doctors might otherwise miss. When a young adult has repeated episodes of confusion or behavioral problems, doctors typically look for common causes like infections or drug use. This report shows that a rare genetic condition should also be considered, especially when ammonia levels are unusually high. The detailed documentation helps other doctors around the world recognize similar patients and start treatment quickly, potentially preventing serious brain damage.
This is a case report, which is a lower level of evidence than large clinical trials but appropriate for describing rare conditions. The strength of this report comes from the genetic confirmation of the diagnosis using two different sequencing methods, detailed clinical documentation, and follow-up data showing treatment response. The limitation is that only two patients are described, so we cannot draw broad conclusions about how common this condition is or how it affects all patients. However, the genetic testing provides strong evidence that these patients truly have the condition described.
What the Results Show
Both patients presented with recurrent episodes of confusion and behavioral disturbances linked to elevated ammonia levels in their blood. The first patient, age 21, had a history of jaundice as a newborn, mild liver scarring, and severe behavioral problems. The second patient, age 18, was noticeably thin and had no visible liver disease, yet still experienced dangerous ammonia spikes.
Genetic testing revealed that both patients carried the identical rare mutation in the SLC25A13 gene, inherited from both parents. This gene normally helps the body process a compound called citrulline, which is essential for removing ammonia from the blood. When this gene is defective, ammonia accumulates to toxic levels.
Interestingly, both patients had lifelong preferences for eating protein and fat while avoiding carbohydrates. This unusual dietary pattern may have contributed to their symptoms, as carbohydrate restriction can worsen ammonia buildup in people with this condition.
When doctors started treatment with ammonia-lowering medications and adjusted the patients’ diets to include more carbohydrates and medium-chain triglycerides (a special type of fat), both patients improved dramatically. Neither patient experienced another encephalopathic episode during the 6-month follow-up period.
The first patient’s history of neonatal jaundice suggests the genetic condition may have been present from birth but went undiagnosed for years. The second patient’s markedly lean appearance may reflect the metabolic stress his body experienced from the genetic defect. Both patients’ unusual food preferences, which seemed random before diagnosis, actually reflected their bodies’ attempt to manage the genetic disorder through dietary choices. The absence of significant liver disease in the second patient is particularly important because it shows that this condition can cause dangerous ammonia buildup even when the liver appears healthy on standard tests.
Citrin deficiency was previously thought to primarily affect infants and young children. This case report adds to growing evidence that the condition can persist into adolescence and adulthood, sometimes going unrecognized for years. Previous research suggested that adult-onset cases would show obvious liver disease, but these patients demonstrate that significant ammonia problems can occur with minimal liver damage. The genetic mutation identified in both patients is the same one reported in other Asian populations, suggesting this may be a more common cause of unexplained ammonia problems in certain ethnic groups than previously recognized.
This report describes only two patients, so we cannot determine how common this condition is or whether all patients respond equally well to treatment. The follow-up period was only 6 months, so we do not know if the improvement continues long-term. The patients are both young Vietnamese men, so results may not apply to other age groups or ethnic backgrounds. The report does not include detailed information about the exact dosages of medications used or specific dietary compositions, which would help other doctors replicate the treatment approach. Additionally, this is a case report rather than a controlled study, so we cannot prove that the treatment caused the improvement rather than other factors.
The Bottom Line
Doctors should consider testing for citrin deficiency in adolescents and young adults with unexplained recurrent episodes of confusion, behavioral changes, or brain problems accompanied by elevated ammonia levels, especially when liver function tests appear relatively normal. Treatment should include ammonia-lowering medications and dietary management emphasizing carbohydrates while limiting protein and fat. Patients should work with a metabolic specialist or genetic counselor to develop an appropriate long-term dietary plan. This recommendation is based on limited evidence from two case reports, so individual treatment plans should be customized by medical professionals.
This finding is most relevant to neurologists, hepatologists, and emergency room doctors who treat patients with unexplained brain symptoms. Genetic counselors should be aware of this condition when counseling families with a history of unexplained neuropsychiatric episodes. Patients with a family history of ammonia-related brain problems or unusual food preferences should discuss testing with their doctors. However, because this is an extremely rare condition, the vast majority of people with confusion or behavioral problems have other causes and should not assume they have citrin deficiency.
Based on these two cases, patients showed clinical improvement within weeks to months of starting appropriate treatment, with no recurrent episodes during 6 months of follow-up. However, long-term outcomes beyond 6 months are unknown. Patients should expect to work closely with their medical team to adjust medications and diet over time. The timeline for diagnosis may be lengthy, as this condition is rare and often misdiagnosed initially.
Frequently Asked Questions
What causes ammonia to build up in the brain and cause confusion?
In citrin deficiency, a faulty gene prevents the body from properly removing ammonia through the normal metabolic pathway. Ammonia accumulates in the blood and crosses into the brain, causing swelling, confusion, and behavioral changes. The liver may appear healthy despite this dangerous ammonia buildup.
Can citrin deficiency be cured or only managed?
Currently, citrin deficiency cannot be cured, but it can be effectively managed through lifelong dietary modifications and ammonia-lowering medications. Treatment focuses on preventing ammonia spikes by emphasizing carbohydrates while limiting protein and fat intake, combined with medication support.
How is citrin deficiency diagnosed if liver tests appear normal?
Diagnosis requires genetic testing, specifically whole-exome sequencing or targeted SLC25A13 gene testing, combined with blood ammonia measurements during symptomatic episodes. Unusual dietary preferences and recurrent unexplained neuropsychiatric symptoms in young adults should prompt testing, even with normal liver function.
Is citrin deficiency inherited and can it be passed to children?
Yes, citrin deficiency is autosomal recessive, meaning a person must inherit the faulty gene from both parents to develop the condition. If both parents are carriers, each child has a 25 percent chance of having the disorder and a 50 percent chance of being a carrier.
What foods should people with citrin deficiency avoid or eat more of?
People with citrin deficiency should eat more carbohydrate-rich foods while limiting high-protein and high-fat foods. Medium-chain triglycerides, a special type of fat, are often recommended. A metabolic specialist should create an individualized meal plan, as dietary needs vary by patient.
Want to Apply This Research?
- Track ammonia levels (if available through home testing or regular lab work), episodes of confusion or behavioral changes, dietary composition (carbohydrate versus protein-fat intake), and medication adherence. Record the date, time, and severity of any neuropsychiatric symptoms alongside ammonia measurements to identify patterns.
- Users with confirmed citrin deficiency should log daily meals to monitor carbohydrate intake and ensure adequate carbohydrate consumption while limiting excessive protein and fat. Set reminders for ammonia-lowering medications and track any neuropsychiatric symptoms to identify triggers. Users can photograph meals or use food logging features to maintain dietary consistency.
- Establish a baseline of normal ammonia levels and symptom-free periods, then track deviations. Create alerts for medication refills and scheduled lab work. Monitor trends over 3 to 6-month periods to assess whether current dietary and medication strategies remain effective. Share tracked data with healthcare providers during regular appointments to guide treatment adjustments.
This article describes a rare genetic condition based on two case reports. It is not a substitute for professional medical advice, diagnosis, or treatment. If you experience recurrent episodes of confusion, behavioral changes, or neuropsychiatric symptoms, consult a healthcare provider immediately. Genetic testing and specialized metabolic evaluation should only be performed under medical supervision. Treatment decisions must be individualized by qualified healthcare professionals, including metabolic specialists or geneticists. This information is for educational purposes only and should not be used for self-diagnosis or self-treatment.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.