Something fishy going on

Dear Editor, A 29 year old Caucasian electrician was referred to the ED by his GP with a 4 day history of an offensive ‘fishy’ body odour. His GP was keen to exclude renal or hepatic dysfunction. The patient had no associated symptoms and had never had a problem like this in the past. He confirmed that he was meticulous with personal hygiene having several showers a day since the problem began. There was no significant family history. Although he felt physically well, the patient was suffering significant social distress because of his condition – his wife had been keeping her distance and he had received complaints from customers at his workplace. His medical history included depression and multiple right knee arthroscopies. He took citalopram 20 mg daily, iron supplements and diazepam for anxiety. He had been taking ‘Musashi Fat Mobilising Formula’ as a weight-loss gym supplement for the previous 6 weeks. He was on no other over-the-counter (OTC) medications or supplements. He was an ex-smoker and drank occasionally. Physical examination was unremarkable except for an offensive rotting fish body odour that was perceptible by all people in the same room as the patient. Blood tests including haematology, renal function, electrolytes and liver function were all within normal range. His urine sample was offensive in odour; however, dipstick and subsequent culture were negative. We began to consider the rare diagnosis of ‘fish odour syndrome’. Urine was sent away for urinary trimethylamine levels to confirm the hypothesis. Subsequent results revealed a grossly elevated trimethylamine : creatinine ratio and trimethylamine : trimethylamine Noxide ratio leading to the diagnosis of trimethylaminuria also known as fish odour syndrome (Table 1). Primary trimethylaminuria is a socially distressing, inherited inborn error of choline metabolism. Affected individuals have a distinct ‘rotting fish’ body odour. It is due to a deficiency in the FMO3 enzyme that metabolises the malodourous amine trimethylamine (TMA) to the non-odorous trimethylamine Noxide (TMAO). Mutations on the FMO3 gene lead to elevated levels of the substrate TMA. Trimethylaminuria incidence is thought to be between one in 100 and one in 1000. There are at least 20 reported mutations of the FMO3 gene and phenotype relates to the severity of the polymorphism. Complete FMO3 inactivating mutations result in extreme and persistent malodour, while less severe polymorphisms decrease the substrate threshold for developing symptoms. Trimethylaminuria may also occur in individuals who have no familial or personal history of the disorder. In these cases, a combination of factors including dietary, hormonal, gut metabolism and enzyme expression are thought to play a role. TMA precursors are derived from dietary sources of choline, lecithin (legumes, organ meats and eggs) and TMAO (marine fish). Gut bacteria converts the precursors to TMA and then the FMO3 gene metabolises TMA to TMAO in the liver. There are some secondary cases of trimethylaminuria reported in the literature where excessive dietary precursor load has led to saturation of the FMO3 enzyme pathway and a subsequent accumulation of the malodorous TMA. Our patient had been on the weight-loss supplement ‘Musashi Fat Mobilising Formula’ for the past 6 weeks. This supplement contains 990 mg choline bitartrate (41% choline by weight) per dose and the patient had been taking two doses a day – equivalent to 810 mg pure choline ingestion per day. The average recommended daily choline intake for an adult male is 550 mg. The supplement also contains acetyl L-carnitine, which can similarly be converted to TMA by gut bacteria (Table 2). We hypothesised that the patient had a mild FMO3 mutation that had previously caused him no issue until he saturated his enzyme pathway with the increased precursor load present in the weight-loss supplement. The patient was advised to cease the supplement and to limit dietary choline sources. Fortunately for the patient (and his wife and employer), after following our advice, 1 month later the fishy odour had completely resolved. We reiterate the importance of taking a thorough drug history