Trimethylaminuria: what is it, symptoms and treatment, prognosis

What is trimethylaminuria?

Trimethylaminuria (fishy odor syndrome) Is a rare disease in which the body's metabolic processes cannot alter the chemical trimethylamine. Trimethylamine has an unpleasant odor. This is the chemical that gives rotten fish an unpleasant odor. When the normal metabolic process fails, trimethylamine builds up in the body and its odor is found in the person's sweat, urine and breath. The effects of foul odor can cause serious social and psychological damage to adolescents and adults.

The genetic or primary form of this disease is transmitted in an autosomal recessive manner. Metabolic deficiency occurs as a result of the inability of the cell to produce a specific protein, in this case the enzyme flavin-containing monooxygenase 3 (eng. flavin-containing monooxygenase 3 [FMO3]). Enzymes are natural catalysts and accelerate biochemical processes. Without the FMO3 enzyme, foods containing carnitine, choline and / or trimethylamine N-oxide are converted to trimethylamine and no longer contain it, causing a strong fishy odor.

The secondary form of trimethylaminuria can result from side effects of treatment with high doses of the amino acid derivative L-carnitine (levocarnitine) or choline. This secondary form of the disorder is the result of trimethylamine overload. In this case, the enzyme is not enough to get rid of the excess trimethylamine.

Signs and symptoms

Fish smell is an obvious symptom; otherwise the patients appear normal and healthy.

Trimethylamine is usually formed as a result of bacterial action in the intestine on choline (found in foods such as soy, liver, kidney, wheat germ, brewer's yeast and egg yolk) or trimethylamine N-oxide (found in marine fish). Then trimethylamine is transferred to liver, where it turns into trimethylamine N-oxide, an odorless metabolic product.

When secondary trimethylaminuria develops as a result of taking large doses of L-carnitine, choline, or lecithin by mouth, symptoms disappear when the dosage of these substances is reduced. L-carnitine is used in the treatment of carnitine deficiency syndromes and is sometimes used by athletes who believe it increases physical strength. Choline is used in treatment Huntington's disease and Alzheimer's disease. Choline and lecithin are found in some supplements and healthy foods.

Causes

Primary trimethylaminuria is a rare metabolic disorder that is inherited as an autosomal recessive genetic trait.

Secondary trimethylaminuria results from treatment with high doses of dietary precursors of the disturbing chemical. Symptoms develop when the ability of the hepatic enzyme (flavin-containing monooxygenase 3) to break down (metabolize) trimethylamine is inhibited.

The responsible gene was designated as FMO3. Although a person has multiple genes FMO, changes in only one of them, FMO3cause trimethylaminuria. For unclear reasons, there are many different changes (mutations) of the gene FMO3.

Genetic diseases are defined by a combination of genes for a specific trait that are found on chromosomes received from the father and mother.

Recessive genetic disorders occur when a person inherits the same abnormal (pathological) gene for the same trait from each parent. If a person receives one normal gene and one gene for the disease, he will be a carrier of the disease, but usually asymptomatic. The risk for two carrier parents of passing on the altered gene and therefore having a sick child is 25% with each pregnancy. The risk of having a child who will be a carrier, like the parents, is 50% with each pregnancy. The probability that a child will receive normal genes from both parents and be genetically healthy for this trait is 25%. The risk is the same for men and women.

All humans carry several abnormal genes. Parents who are close relatives (blood relatives) are at higher risk than unrelated parents parents both of whom carry the same abnormal gene, which increases the risk of having children with recessive genetic disease.

Affected populations

Trimethylaminuria is a rare metabolic disorder. More than 100 cases have been described in the medical literature. Some doctors believe that the condition is underdiagnosed because many with mild symptoms do not seek help. However, some doctors do not recognize the symptoms of trimethylaminuria when a person with an unpleasant body odor seeks help with diagnosis.

Diagnostics

The smell of rotten fish is indicative, especially in severe cases. However, a diagnosis based on odor is unreliable because odor is often sporadic and not everyone can detect the odor of trimethylamine. In addition, the odor of trimethylaminuria can be difficult to distinguish from other conditions that cause body odor. Diagnosis is based on urinalysis to trimethylamine and trimethylamine N-oxide, which distinguishes between severe and mild cases. Urinalysis after taking large doses of trimethylamine can distinguish carriers of the disease from healthy patients. Genetic testing is available to distinguish primary genetic trimethylaminuria, which leads to severe symptoms, from secondary non-genetic forms of the disease.

Standard treatments

In mild cases, symptoms are relieved by limiting the intake of foods containing choline and lecithin. In some severe cases, it may be necessary to administer an antibiotic that sterilizes the intestines, such as metronidazole. This treatment reduces the number of gut bacteria that break down choline and trimethylamine N-oxide to trimethylamine. In the case of mutations that do not completely abolish FMO3 activity, riboflavin supplementation can help maximize the residual enzyme activity. Food additives such as activated carbon and copper chlorophyllin can bind trimethylamine in the intestine and therefore reduce the amount available for absorption. Using mildly acidic soaps and body lotions can convert the trimethylamine on the skin to a less volatile form that can be removed by washing. If the disorder is due to excessive doses of L-carnitine, choline, or lecithin, symptoms disappear as the dosage is reduced.

Genetic counseling can be helpful for patients and their families.

Forecast

Many people with trimethylaminuria, especially those with mild to moderate symptoms, will be able to reduce fish odor through dietary and lifestyle changes. Trimethylaminuria does not cause any other physical health problems, and people with the disease are generally healthy otherwise.