Trimethylaminuria

What is Trimethylaminuria?

Trimethylaminuria (TMAU), often called fish odor syndrome or stale fish syndrome, is a rare health condition. It’s linked to abnormal buildup and release of a compound called trimethylamine (TMA) in the body. TMA leads to a strong, foul smell similar to that of rotting fish.

Trimethylaminuria usually happens because of a problem with a specific liver enzyme known as flavin-containing monooxygenase 3 (FMO3). This enzyme’s job is to change TMA into a different, smell-free compound called trimethylamine N-oxide (TMAO).

It’s also worth mentioning that TMA has a strong fishy smell and can act as a pheromone, a kind of chemical signal, in various organisms. Although this condition was first officially reported in 1970, it is likely that trimethylaminuria has been around for much longer.

What Causes Trimethylaminuria?

Primary Trimethylaminuria

Trimethylaminuria is a condition that can occur because of a change or mutation in a specific gene named FMO3. This gene is on a structure in our cells called chromosome 1q24.3. Different changes to this gene can result in the FMO3 protein not working properly, including less activity, difficulty attaching to other molecules, or disrupting the protein structure. People typically get trimethylaminuria when both copies of the FMO3 gene they inherit (one from each parent) have these changes. However, there are rare cases where only one copy of the FMO3 gene is changed, which can still lead to some degree of trimethylaminuria.

This condition affects how the body breaks down a compound called TMA. When TMA isn’t broken down properly, it builds up in the body and is released through urine, sweat, and breath, resulting in a fishy smell.

In some rare cases, trimethylaminuria is caused by a problem with the body’s metabolism due to a lack of an enzyme called dimethylglycine dehydrogenase. This lack of enzyme results in a significant increase in another compound called N,N-dimethylglycine (DMG) in the blood and urine, which can also cause a fishy smell.

Secondary Trimethylaminuria

Secondary trimethylaminuria is another type of trimethylaminuria where the body’s enzymes are functioning but can become overwhelmed due to too much of certain dietary compounds. This can result in an excess amount of TMA. The dietary compounds that can cause this are found in eggs, beans, and peas (choline) and red meats and fish (carnitine). Some people consume extra carnitine for better physical performance. Choline is used to treat Alzheimer’s and Huntington’s diseases.

These dietary compounds are turned into TMA by bacteria in the colon. The TMA is then absorbed into the body and has to be broken down by the liver. If the liver can’t handle all the TMA, symptoms of trimethylaminuria can develop.

In addition to the dietary factors, liver failure, certain medical conditions that affect blood flow through the liver, menstruation, viral hepatitis, and testosterone therapy are other possible causes of secondary trimethylaminuria.

Risk Factors and Frequency for Trimethylaminuria

TMAU, or trimethylaminuria, is a condition that is estimated to affect 1 in 200,000 to 1 in 1,000,000 people around the world. However, because many people aren’t aware of the condition and it often isn’t diagnosed, there could be significantly more people who have it. Certain groups may have greater rates of TMAU, such as people with Ashkenazi Jewish ancestry, and about 11% of New Guineans are carriers of the condition.

Both men and women can have TMAU, though some research suggests that women might experience more intense symptoms due to the hormonal changes that happen during their menstrual cycles and pregnancies. Although people can develop TMAU at any age, the symptoms usually become more obvious during puberty, which is another time of significant hormonal change.

Signs and Symptoms of Trimethylaminuria

Trimethylaminuria (TMAU) is a health condition known for causing certain distinct symptoms. These include a smell resembling fish in body odor, bad breath, and strong-smelling urine. Carrying this condition can have serious emotional and social consequences as the scent can be overpowering and unpredictable, potentially leading to feelings of embarrassment, social withdrawal, low self-confidence, and even depression.

The most obvious symptom of TMAU is a strong, unpleasant body odor that can be reminiscent of rotting fish. This smell can appear anytime from the moment of birth to puberty. Interestingly, not all individuals with TMAU or those around them can detect the odor. The smell primarily stems from the release of a substance called trimethylamine (TMA) in sweat, breath, urine, and other body secretions. The intensity of this odor can vary, sometimes based on eating habits, stress, hormone fluctuations, and medication use. The smell can range from fishy to musty or similar to ammonia, particularly after eating foods with high TMA content.

• Fishy body odor
• Unpleasant breath
• Musty or ammonia-like smell
• Smell intensity variation

People with TMAU may also suffer from halitosis, or bad breath, due to the release of TMA in the breath, adding to the offensive odor. Similarly, their urine can have a unique, fishy, or ammonia-like smell.

Testing for Trimethylaminuria

To diagnose trimethylaminuria (TMAU), a condition that makes your sweat and urine smell like rotten fish, a combination of medical evaluation, and specific specialized tests are used.

The process starts with laboratory tests on your urine. In this case, the lab will look for elevated levels of trimethylamine (TMA), a chemical compound that could indicate you are having trouble metabolizing and that’s what could be causing the unpleasant smell.

To confirm this, you might need to take a TMA challenge or load test. This test involves consuming a large dose of TMA, which is found in certain types of marine fish. After that, your urine will be tested at several points within 2 to 12 hours. People with trimethylaminuria will have higher levels of TMA in their urine after this test.

The activity of an enzyme called FMO3 can also be checked through a blood sample. The FMO3 enzyme is responsible for breaking down TMA in your body. If this enzyme is not as active as it should be, or completely absent, it can lead to a build-up of TMA – another potential symptom of trimethylaminuria.

Lastly, genetic tests may be used to look for specific mutations in the FMO3 gene. These tests use blood or saliva samples to find genetic changes tied to trimethylaminuria. By identifying these, the doctors can confirm if you have the condition, figure out the specific genetic mutation causing it, and understand how the disorder may be inherited.

Treatment Options for Trimethylaminuria

Treatment for the condition Trimethylaminuria (also known as TMAU) is focused on easing symptoms and improving the individual’s quality of life, as there currently is no cure for it. A questionnaire has been specifically designed to assess how effective treatment has been for the patient. It includes a range of health-related questions to assess various aspects of the condition’s impact. Several treatment options are available for TMAU, these include changes in diet, antibiotic therapy, using activated charcoal, maintaining personal hygiene, and getting psychological support.

Making changes in your diet is often suggested to reduce symptoms. This means limiting or stopping eating foods that are high in choline, carnitine, and TMAO. This can include certain types of fish, red meats, liver, eggs, legumes, and some vegetables. It can be helpful to work with a dietitian who specializes in metabolic disorders to create a suitable meal plan for you.

Sometimes, low-dose antibiotics are prescribed to decrease the amount of bacteria in the gut that produce TMA – the compound that causes the smell associated with TMAU. Antibiotics like neomycin and metronidazole have been used successfully in some cases. However, it’s important that long-term use of antibiotics is carefully monitored due to possible side effects and the risk of developing resistance to the antibiotic.

Activated charcoal, which is able to absorb and reduce TMA levels in the gut, may be used as a supplement to help decrease TMA production. However, how effective this is can differ from person to person.

Copper chlorophyllin, a compound derived from chlorophyll, has been used as a supplement to help decrease body odor. It’s thought that copper chlorophyllin can neutralize odor-causing compounds. However, its effectiveness in managing TMAU symptoms is still being researched, and its effects can vary between individuals.

Maintaining good personal hygiene can help manage the odor associated with TMAU. This can include regularly bathing or showering with soaps or body washes designed to reduce body odor.

TMAU can significantly affect a person’s self-esteem and mental health. Seeking support from mental health professionals, participating in support groups, and getting counseling can all help manage the emotional and psychological aspects of living with TMAU.

A recent study found that a treatment called ‘endovascular closure’, when performed between birth and 21 years old on patients who have congenital portosystemic shunts (a condition where the liver’s blood supply is disrupted), resolved TMAU symptoms.

What else can Trimethylaminuria be?

When a doctor is exploring the possibility of a patient having a condition called TMAU, they need to take into account other conditions that could potentially causing similar symptoms. These could be genetic, systemic, or specific diseases or disorders.

• Vaginal conditions such as bacterial vaginosis or trichomoniasis could cause a smell that’s like TMAU. Doctors can identify these conditions using various methods, which could include checking the genitals, testing the pH, or looking at vaginal secretions under a microscope. There are also other types of testing available.
• Some types of food, like seafood, could result in a temporary body smell that resembles TMAU. This smell would disappear when the food causing the smell has been fully digested and removed from the body. To tell this apart from TMAU, you would need to look closely at what a patient has been eating and whether there’s any pattern connecting this with when symptoms are appearing.
• Issues with the liver or kidneys could cause changes in body smell. If you have liver disease, such as cirrhosis or a deficiency in liver enzymes, you could end up with a smell that’s fishy or smells like ammonia.
• There are also certain metabolic disorders could result in odd body smells. For example, isovaleric acidemia, which is a genetic disorder, can cause an unusual smell reminiscent of sweaty feet. Others could lead to smells like maple syrup or musty odors. Doctors can use metabolic screening tests in order to rule these out.
• Changes in hormones, such as puberty, periods, or pregnancy, can cause changes in body smell. At these times, changes in sweat make-up and amount could sometimes result in a fishy smell. A closer look at whether these changes and symptoms show up at the same time can help identify if hormones are causing body smell rather than trimethylaminuria.
• Poor hygiene can also cause body odors. If a person bathes infrequently or doesn’t use hygiene products correctly, they could end up with a body odor.

What to expect with Trimethylaminuria

Trimethylaminuria (TMAU), while chronic and currently incurable, is not a condition that threatens life. With the right care and support, many people with TMAU can live satisfying lives. Keeping to regular check-ups with healthcare professionals who specialize in metabolic disorders is crucial. Similarly, faithfully following treatment plans and making healthy lifestyle choices can help individuals control their symptoms and improve their long-term health outlook.

Possible Complications When Diagnosed with Trimethylaminuria

TMAU is associated with a particular fishy smell that can cause substantial emotional and societal stress. This odor can cause people with TMAU to feel embarrassed and isolated, and it can make them have low self-worth because the smell is persistent and unpredictable.^[16] The societal stigma can put them at risk of developing anxiety and depression.^[2] These emotional and psychological challenges can have an enormous impact on personal relationships, job prospects, and the overall quality of life.

Effects of TMAU:

• Significant emotional and societal stress
• Feelings of embarrassment and isolation
• Low self-esteem
• Risk of anxiety and depression
• Impact on personal relationships
• Effect on job opportunities
• Decrease in overall quality of life

Preventing Trimethylaminuria

Educating patients is crucial in managing Trimethylaminuria (TMAU), a metabolic condition that causes a strong body odor. This means teaching individuals about TMAU and giving them methods to handle the challenges that come with it. Education can be done in several ways.

One important method is through one-on-one sessions with healthcare professionals such as genetic experts, metabolic specialists, or diet experts. These sessions provide personalized information about TMAU. Here, the healthcare professional addresses each person’s unique needs, concerns, and questions. During these sessions, patients can learn about changes in diet, proper hygiene practices, treatment methods, and how to cope with TMAU.

Another way is through group education or support groups, where people with TMAU can come together, share experiences, learn from each other, and get information from healthcare professionals. These types of sessions not only provide information, but also reduce feelings of loneliness by creating a supportive community.

Finally, there are mobile applications developed specifically for individuals with TMAU. These apps can be used to access educational resources, track diet, remind about hygiene practices, and participate in community conversations, all from the convenience of a mobile phone. These apps help individuals keep track of their symptoms, monitor their food intake, and get personalized advice about managing their condition.