Treatment
There is no known permanent cure or treatment for primary trimethylaminuria, only mitigation of the effects. For secondary trimethylaminuria, it depends on the cause; for precursor overload, reducing the intake of TMA and its precursors will end symptoms. For TMAU caused by hypothetical gut dysbiosis, clinical review by a doctor, a plant based diet and reduced precursor intake should return gut flora to a healthy state.Primary TMAU sufferers generally have some residual FMO3 activity in the liver which processes TMA, however this happens relatively slowly. According to a study by Al-Waiz M TMA filters through to the bladder at half the rate of TMAO, and a healthy functioning person passes 99% of TMAO in urine within 24 hours. Therefore its estimated that the majority of TMA would be filtered out within 48 hours if no additional TMA or precursor is ingested, regardless of liver function. The metabolic and clinical manifestations of TMAU are generally regarded as benign, as there is no associated organ dysfunction. This designation, and the fact that the condition is often unrecognised by doctors, misdiagnosed and can have important ramifications including missed or delayed diagnosis.Affected individuals experience shame and embarrassment, fail to maintain relationships, avoid contact with people who comment on their condition, and are obsessive about masking the odour with hygiene products and even smoking. The malodorous aspect can have serious and destructive effects on schooling, personal life, career and relationships, resulting in social isolation, low self-esteem, depression, paranoid behaviour, and suicide.
In women, symptoms may worsen just before and during menstrual periods, after taking oral contraceptives, and around menopause.The odor seems to vary depending on many known factors, including diet, hormonal changes, stress level, amount of sweat, other odors in the space, and the observers sense of smell. Genetics
Most cases of trimethylaminuria appear to be inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. The parents of an individual with an autosomal recessive disorder are both carriers of one copy of the altered gene. Carriers may have mild symptoms of trimethylaminuria or experience temporary episodes of fish-like body odor.Mutations in the FMO3 gene, which is found on the long arm of chromosome 1, cause trimethylaminuria. The FMO3 gene makes an enzyme that breaks down nitrogen-containing compounds from the diet, including trimethylamine. These compounds are produced by bacteria in the intestine as they digest proteins from eggs, meat, soy, and other foods. Normally, the FMO3 enzyme converts fishy-smelling trimethylamine into trimethylamine N-oxide which has no odor. If the enzyme is missing or its activity is reduced because of a mutation in the FMO3 gene, trimethylamine is not broken down and instead builds up in the body. As the compound is released in a persons sweat, urine, and breath, it causes the strong odor characteristic of trimethylaminuria. Researchers believe that stress and diet also play a role in triggering symptoms.There are more than 40 known mutations associated with TMAU.