Trimethylaminuria syndrome

Fig. 7.4.2 The origin and metabolism of TMA in man. This figure shows the molecular defect in the flavin-containing mono-oxygenase ( ) in trimethylaminuria or fish odour syndrome. The dashed line indicates the minor metabolic pathway in healthy volunteers. Enzyme steps marked with B are in the intestinal bacterial flora. DMA Dimethylamine, MMA monomethyl-...

Fish odour syndrome is an autosomal recessive disease. Mutations have been found in the FM03 gene. Molecular genetic analysis can therefore be used as a diagnostic test. Many pathogenic mutations have been described. The defect should be documented in patients with trimethylaminuria at the metabolite level and the diagnosis confirmed at the molecular genetic level. This chapter describes the available tests at the metabolite level. 

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NMR spectroscopy can be used to find inborn errors of metabolism characterised by the presence of metabolites that cannot be detected with conventional screening methods. Trimethylaminuria or fish odour syndrome may serve as an example [9]. It is a hereditary disease based on an enzyme deficiency in the liver. Trimethylamine (=TMA) derives from bacteria that convert it from dietary choline. Normally there is an enzyme in the liver that oxidizes TMA efficiently. TMA and trimethylamine N-oxide (=TMAO) are both secreted in the urine. TMA has the smell of rotten fish causing a social problem for the patient. Until recently no technique could measure TMA and TMAO simultaneously to prove this deficiency at the metabolic level. This is very well possible with NMR spectroscopy. 

Tauri disease Tay-Sachs disease Testicular feminization syndrome Tetrahydrobiopterin deficiency Thiopurine methyltransferase deficiency Thymidine phosphorylase deficiency Transcobalamin II deficiency Tricho-hepato-enteric syndrome Trimethylaminuria Tripeptidyl peptidase I deficiency Tryptophan-2,3-dioxygenase deficiency Tryptophanuria... 

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