There are three types of trimethylaminuria:

PRIMARY TRIMETHYLAMINURIA (TMAU1)

It is due to mutations in the FMO3 gene, inherited in an autosomal recessive manner. This means that both copies of the gene have the mutation. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but typically show no signs and symptoms of the condition. However, heterozygous carriers of an FMO3 mutation may have mild symptoms of trimethylaminuria or experience temporary episodes of body odour.

Under normal conditions, TMAO and TMA precursors, such as choline, taken with the diet, are reduced to TMA by the anaerobic bacterial flora present in the colon. TMA passively diffuses across cell membranes and enters the enterohepatic circulation to be metabolized in the liver. Here FMO3 oxidizes the TMA to TMAO. In affected individuals, the functional deficit of FMO3 causes an accumulation of trimethylamine following the introduction of foods rich in choline (meat, liver, eggs and beans / peas), L-carnitine, betaine and lecithin.

SECONDARY TRIMETHYLAMINURIA (TMAU2)

There are a secondary or acquired forms in which the excretion of TMA is high even if the activity of the FMO3 enzyme is normal. Most patients with TMAU2 produce high levels of TMA due to an excessive growth of the bacterial species that generate TMA. This problem can be exacerbated by intestinal structural problems such as 'blind loops' or post-operative complications.

TMAU2 can also occur after the therapeutic administration of choline for the treatment of Huntington's disease and Alzheimer's disease. Liver diseases, such as viral hepatitis, can be another cause as well as portosystemic shunt and severe impairment of hepatocellular function.
In addition, trimethylaminuria can be accompanied by chronic kidney disease or urinary tract infections that cause TMA to be produced directly in the urine, causing a false positive result.

TRANSITIONAL FORMS OF TMAU

Transient forms of TMAU can occur in childhood when FMO3 expression levels are minimal and in the perimenstrual period when steroid hormones can cause decreased FMO3 expression. The intermittent forms can be due to sweating and excessive exercise, fever, stress, emotional disturbances.