Inheritance patterns

Trimethylaminuria (TMAU) follows an autosomal recessive inheritance pattern, meaning that affected individuals inherit two copies of a mutated gene, one from each parent, in order to manifest the condition.

The gene primarily implicated in TMAU is the flavin-containing monooxygenase 3 (FMO3) gene, located on chromosome 1q24.3.

This gene encodes the enzyme FMO3, which is responsible for the oxidation of trimethylamine (TMA) to its non-odorous metabolite, trimethylamine N-oxide (TMAO), in the liver. Mutations in the FMO3 gene result in reduced or impaired enzyme activity, leading to the accumulation of TMA and subsequent malodor production characteristic of TMAU.

Individuals who inherit one mutated copy of the FMO3 gene (heterozygous carriers) typically do not exhibit TMAU symptoms, as they still possess sufficient enzyme activity to metabolize TMA adequately.

However, when both copies of the FMO3 gene are mutated (homozygous or compound heterozygous), enzyme function is significantly compromised, resulting in the clinical manifestations of TMAU.

Genetic testing can identify specific mutations in the FMO3 gene, aiding in the diagnosis and genetic counseling of individuals and families affected by TMAU.

Last updated : March 2024