Trimethylaminuria

A hereditary autosomal recessive condition which results from the abnormal presence of large amounts of volatile and malodorous trimethylamine within the body. This chemical, a tertiary aliphatic AMINE, is excreted in the urine, sweat (ichthyohidrosis), and breath, which take on the offensive odor of decaying fish. Mutations in the FMO3 gene have been identified. OMIM: 602079

Also Known As:

Networked: 135 relevant articles (4 outcomes, 11 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Sclerosis
2.	Inflammation (Inflammations)
3.	Colitis
4.	Sudden Infant Death (SID)
5.	Trimethylaminuria

Experts

1.	Yamazaki, Hiroshi: 17 articles (12/2021 - 01/2003)
2.	Shimizu, Makiko: 16 articles (12/2021 - 06/2006)
3.	Cashman, John R: 9 articles (06/2009 - 05/2002)
4.	Shephard, Elizabeth A: 7 articles (01/2020 - 08/2002)
5.	D'Angelo, Rosalia: 6 articles (11/2021 - 02/2013)
6.	Sidoti, Antonina: 6 articles (11/2021 - 02/2013)
7.	Phillips, Ian R: 6 articles (01/2020 - 08/2002)
8.	Scimone, Concetta: 4 articles (11/2021 - 10/2014)
9.	Zhang, Jun: 4 articles (06/2009 - 10/2002)
10.	Kamataki, Tetsuya: 4 articles (01/2007 - 01/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Trimethylaminuria:

1.	trimethyloxamine (trimethylamine N-oxide)IBA 02/01/2011 - "The symptoms of trimethylaminuria can be improved by changes in the diet to avoid precursors, in particular TMAO which is found in high concentrations in marine fish. " 10/01/2021 - "Quality consideration for the validation of urine TMA and TMAO measurement by nuclear magnetic resonance spectroscopy in Fish Odor Syndrome." 01/01/2021 - "Urine test samples with high levels of free TMA and subnormal percentage of trimethylamine N-oxide revealed the diagnosis of trimethylaminuria. " 02/01/2011 - "Diagnosis of trimethylaminuria requires the measurement of TMA and TMAO in urine, which should be collected after a high substrate meal in milder or intermittent cases, most simply, a marine-fish meal. " 01/01/2007 - "The proposed method allows for rapid and reliable measurements of TMA and TMAO in urine specimens from patients affected by trimethylaminuria."
2.	Choline (Choline Chloride)IBA 02/01/2006 - "Loading with a marine fish meal provides a simple and acceptable method for confirmation of diagnosis of suspected trimethylaminuria in children, with the effects being cleared more quickly than with a choline load test. " 02/01/2006 - "We have compared the dynamics and diagnostic efficacy of choline loading with marine fish meals in six children with trimethylaminuria. " 11/01/1985 - "Studies of the patient's urine after choline loading established the diagnosis of trimethylaminuria. " 11/01/2011 - "If so, choline challenge testing should be indicated for all such patients because trimethylaminuria is responsive to dietary and other treatments. " 11/01/2011 - "We tested 353 patients who had unexplained (idiopathic) malodor production for trimethylaminuria using a standard choline challenge. "
3.	Charcoal (Charbon)IBA 01/01/2021 - "Le Carbone (LC), a fiber-enriched activated charcoal dietary supplement, claimed to be effective against inflammation associated with colitis, trimethylaminuria, and sclerosis. " 04/16/2004 - "Effects of the dietary supplements, activated charcoal and copper chlorophyllin, on urinary excretion of trimethylamine in Japanese trimethylaminuria patients."
4.	dimethylaniline monooxygenase (N-oxide forming) (flavin-containing monooxygenase)IBA 06/01/2023 - "Analysis of trimethylaminuria phenotypes in family studies has revealed compound missense FMO3 variants that impair FMO3-mediated N-oxygenation in Japanese subjects; moreover, these variants could result in modified drug clearances." 06/01/2023 - "A family study of compound variants of flavin-containing monooxygenase 3 (FMO3) in Japanese subjects found by urinary phenotyping for trimethylaminuria." 12/01/2015 - "The aim of this study was to screen another self-reported Japanese trimethylaminuria cohort for novel FMO3 variants and to investigate these new variants. " 11/01/2009 - "In this study mutations of the FMO3 gene were examined in self-reported Japanese trimethylaminuria subjects that showed low FMO3 metabolic capacity in urine tests. " 01/01/2007 - "Results from biochemical investigations confirmed a diagnosis of primary trimethylaminuria, and results of molecular genetic studies revealed homozygosity for a mutation on exon 4 of the FMO3 gene, FMO3/P153L (c.458C --> T). "
5.	trimethylamineIBA 08/01/2020 - "This is the first report and characterization of a patient of fish odor syndrome caused by genetic aberrations leading to impaired FMO3-dependent N-oxygenation of trimethylamine found in the Argentinian population. " 01/01/2019 - "Trimethylaminuria (TMAU) is a metabolic disorder characterized by the excessive excretion of the malodorous compound trimethylamine (TMA). " 11/07/2017 - "Certain mutations within the hFMO3 gene cause defective trimethylamine (TMA) N-oxygenation leading to trimethylaminuria (TMAU) also known as fish-odour syndrome. " 01/15/2014 - "Trimethylaminuria is a rare, autosomal recessive, metabolic disorder that results in accumulation of trimethylamine (TMA), which smells like rotten fish. " 01/01/2014 - "Trimethylaminuria (TMAU) is an autosomal recessive disease caused by excessive excretion into body fluids and breath of unoxidized trimethylamine (TMA) derived from the enterobacterial metabolism of dietary precursors. "
6.	4,6-dinitro-o-cresol (DNOC)IBA 04/13/2015 - "Given the suspicion of trimethylaminuria, molecular study of flavin mono-oxygenase 3 gene was requested. " 05/01/2014 - "Relationships between flavin-containing mono-oxygenase 3 (FMO3) genotype and trimethylaminuria phenotype in a Japanese population." 01/01/2013 - "Trimethylaminuria is a malodour syndrome caused by a functional defect of flavin-containing monoxygenase 3 (FMO3), resulting in accumulation of trimethylamine in body secretions. " 03/01/2003 - "Our patient had biochemical analysis consistent with a diagnosis of secondary trimethylaminuria, while analysis of the flavin-containing mono-oxygenase 3 gene, the causative gene in primary trimethylaminuria, demonstrated three sequence polymorphisms, two of which are known to reduce enzyme activity. " 01/01/1999 - "Flavin-containing mono-oxygenase 3 (FMO3) catalyses TMA oxidation and mutations in the FMO3 gene have recently been shown to underlie trimethylaminuria/fish odour syndrome. "
7.	OxygenasesIBA 04/13/2015 - "Given the suspicion of trimethylaminuria, molecular study of flavin mono-oxygenase 3 gene was requested. " 08/01/1997 - "Human Lys158 Ile66 FMO3-MBP, Glu158 Ile66 FMO3-MBP, Lys158 Leu153 FMO3-MBP, and Glu158 Leu153 FMO3-MBP were all constructed as mutants identified as possible FMO3 variants responsible for trimethylaminuria and were found to be inactive as N-oxygenases. " 05/01/2014 - "Relationships between flavin-containing mono-oxygenase 3 (FMO3) genotype and trimethylaminuria phenotype in a Japanese population." 03/01/2003 - "Our patient had biochemical analysis consistent with a diagnosis of secondary trimethylaminuria, while analysis of the flavin-containing mono-oxygenase 3 gene, the causative gene in primary trimethylaminuria, demonstrated three sequence polymorphisms, two of which are known to reduce enzyme activity. " 01/01/1999 - "Flavin-containing mono-oxygenase 3 (FMO3) catalyses TMA oxidation and mutations in the FMO3 gene have recently been shown to underlie trimethylaminuria/fish odour syndrome. "
8.	Betaine (C.B.B.)FDA Link 12/01/2004 - "Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria." 01/01/2012 - "Riboflavin-responsive trimethylaminuria in a patient with homocystinuria on betaine therapy." 09/01/2015 - "A rapid SID-LC-MRM-MS assay for simultaneous quantification of choline, betaine, TMA, TMAO, and creatinine has been developed and validated, and is expected to find wide application in nutrition and cardiovascular studies as well as diagnosis and management of trimethylaminuria."
9.	CreatinineIBA 04/01/2008 - "In five patients with diagnosed trimethylaminuria, TMA was 5.3-230 mmol/mol creatinine, TMAO was 0.36-607 mmol/mol creatinine and the TMA/TMAO ratio was 0.20-134." 09/01/2015 - "A rapid SID-LC-MRM-MS assay for simultaneous quantification of choline, betaine, TMA, TMAO, and creatinine has been developed and validated, and is expected to find wide application in nutrition and cardiovascular studies as well as diagnosis and management of trimethylaminuria."
10.	EnzymesIBA 01/01/2018 - "Trimethylaminuria is caused by a functional enzyme defect and is usually congenital. " 11/05/2010 - "These data rationalize the effect of mutations that cause enzyme deficiency in patients affected by the fish odor syndrome. " 08/15/2007 - "These data demonstrate that primary trimethylaminuria is multifactorial in origin in that enzyme dysfunction can result from kinetic incompetencies as well as impaired assembly of holoprotein." 02/01/2011 - "Primary trimethylaminuria sufferers have an inherited enzyme deficiency where TMA is not efficiently converted to the non-odorous TMAO in the liver. " 09/01/2009 - "Analysis of the mutant FMO3 expressed in bacteria revealed that the R238Q mutation abolished catalytic activity of the enzyme and is thus a causative mutation for TMAuria. "

Therapies and Procedures

1.	Surgical Portasystemic Shunt (Portosystemic Shunt) 11/01/2019 - "This study aimed to report three new cases of an association between two rare conditions, congenital portosystemic shunts (CPSS) and trimethylaminuria (TMAU), and the efficacy of endovascular closure of the CPSS for resolving TMAU. " 11/01/2019 - "Endovascular Closure Resolves Trimethylaminuria Caused by Congenital Portosystemic Shunts."
2.	Palliative Care (Palliative Therapy) 01/01/2009 - "This study investigates foodstuff first in healthy volunteers for palliative care for self-reported Japanese trimethylaminuria subjects. " 01/01/2009 - "These results in healthy volunteers suggest that bonito may be one of the best nutrient sources and palliative care for self-reported Japanese trimethylaminuria subjects." 01/01/2009 - "Bonitos with low content of malodorous trimethylamine as palliative care for self-reported Japanese trimethylaminuria subjects."
3.	Therapeutics 10/01/2019 - "A case of axillary bromhidrosis secondary to trimethylaminuria successfully treated with microwave-based therapy." 01/01/2012 - "Riboflavin-responsive trimethylaminuria in a patient with homocystinuria on betaine therapy."
4.	Nutritional Support (Artificial Feeding) 04/01/2003 - "Finally, trimethylaminuria treatment strategies and nutritional support are described including dietary sources of trimethylamine, vitamin supplementation and drug treatment and issues related to trimethylaminuria in pregnancy and lactation are discussed. "
5.	Gastric Bypass (Roux-en-Y Gastric Bypass) 07/01/2013 - "The fish malodor syndrome: a new indication for gastric bypass surgery?"