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Tidsskrift For Den Norske Laegeforening... Sep 2021Trimethylaminuria is a rare disorder characterised by foul odour from bodily fluids and breath. The condition is caused by a homozygous mutation in the FMO3 (flavin...
BACKGROUND
Trimethylaminuria is a rare disorder characterised by foul odour from bodily fluids and breath. The condition is caused by a homozygous mutation in the FMO3 (flavin monooxygenase 3) gene coding for the enzyme that converts TMA (trimethylamine) to trimethylamine N-oxide. The result is elevated levels of secreted trimethylamine, which has a strong odour. The condition is likely to affect mental, emotional and social health. The diagnosis is reached by testing of free TMA (trimethylamine) and percentage N-oxidation in urine samples or by genetic testing.
CASE PRESENTATION
A man in his fifties had from childhood occasionally been told that his breath resembled rotten fish. He had searched for a diagnosis on the internet and was referred to testing for trimethylaminuria, and the diagnosis was confirmed.
INTERPRETATION
Urine test samples with high levels of free TMA and subnormal percentage of trimethylamine N-oxide revealed the diagnosis of trimethylaminuria. There is no causal treatment. Patients are advised to avoid choline-rich foods and take hygienic measures.
Topics: Animals; Child; Fishes; Humans; Male; Metabolism, Inborn Errors; Methylamines; Mutation; Oxygenases
PubMed: 34597008
DOI: 10.4045/tidsskr.21.0142 -
BMJ Case Reports Apr 2016We report the case of a 9-year-old boy referred to secondary care with an unusual presentation of a fishy odour to his hands, feet, saliva and urine. Laboratory...
We report the case of a 9-year-old boy referred to secondary care with an unusual presentation of a fishy odour to his hands, feet, saliva and urine. Laboratory investigations including urine analysis and genetic testing confirmed the diagnosis of trimethylaminuria. The patient was referred to a geneticist and dietician, and consequently treated with dietary modification. He now has an arguably much improved quality of life.
Topics: Animals; Child; Fishes; Foot; Genetic Testing; Hand; Humans; Male; Metabolism, Inborn Errors; Methylamines; Odorants; Quality of Life; Saliva; Urinalysis
PubMed: 27118741
DOI: 10.1136/bcr-2015-213742 -
Drug Discovery Today Sep 2020Trimethylamine (TMA) is a volatile, foul-smelling, diet-derived amine, primarily generated in the colon and metabolized in the liver to its odorless N-oxide (TMAO). In... (Review)
Review
Trimethylamine (TMA) is a volatile, foul-smelling, diet-derived amine, primarily generated in the colon and metabolized in the liver to its odorless N-oxide (TMAO). In primary trimethylaminuria (TMAU), an inherited deficiency in flavin-containing monooxygenase 3 leads to elevated systemic TMA levels. The excretion of elevated amounts of TMA in sweat, breath, urine and other bodily secretions gives individuals affected by TMAU a smell resembling that of rotten fish. Although the disorder might not seem an important health problem, its social and psychological burden can be devastating. To date, no treatment modifying the disorder exists and only a few pharmacological therapies provide modest and transient benefits. This review provides an overview of investigated TMAU treatments and outlines promising new research directions.
Topics: Animals; Humans; Metabolism, Inborn Errors; Methylamines; Oxygenases
PubMed: 32615074
DOI: 10.1016/j.drudis.2020.06.026 -
BMC Public Health Jan 2024Many people suffer from body and breath malodour syndromes. One of these is trimethylaminuria, a condition characterized by excretion in breath and bodily fluids of...
BACKGROUND
Many people suffer from body and breath malodour syndromes. One of these is trimethylaminuria, a condition characterized by excretion in breath and bodily fluids of trimethylamine, a volatile and odorous chemical that has the smell of rotting fish. Trimethylaminuria can be primary, due to mutations in the gene encoding flavin-containing monooxygenase 3, or secondary, due to various causes. To gain a better understanding of problems faced by United Kingdom residents affected by body and breath malodour conditions, we conducted a survey.
METHODS
Two anonymous online surveys, one for adults and one for parents/guardians of affected children, were conducted using the Opinio platform. Participants were invited via a trimethylaminuria advisory website. Questions were a mix of dropdown, checkbox and open-ended responses. Forty-four adults and three parents/guardians participated. The dropdown and checkbox responses were analysed using the Opinio platform.
RESULTS
All participants reported symptoms of body/breath odour. However, not all answered every question. Twenty-three respondents experienced difficulties in being offered a diagnostic test for trimethylaminuria. Problems encountered included lack of awareness of the disorder by medical professionals and reluctance to recognise symptoms. Of those tested, 52% were diagnosed with trimethylaminuria. The main problems associated with living with body/breath malodours were bullying, harassment and ostracism in either the workplace (90%) or in social settings (88%). All respondents thought their condition had disadvantaged them in their daily lives. Open-ended responses included loss of confidence, stress, exclusion, isolation, loneliness, depression and suicidal thoughts. Respondents thought their lives could be improved by greater awareness and understanding of malodour conditions by medical professionals, employers and the general public, and appreciation that the malodour was due to a medical condition and not their fault.
CONCLUSIONS
Breath and body malodour conditions can cause immense hardship and distress, both mentally and socially, having devastating effects on quality of life. It would be advantageous to establish a standardised pathway from primary care to a specialist unit with access to a robust and reliable test and diagnostic criteria. There is a need to recognise malodour disorders as a disability, giving affected individuals the same rights as those with currently recognised disabilities.
Topics: Adult; Child; Animals; Humans; Quality of Life; Metabolism, Inborn Errors; Odorants; Anxiety; Methylamines
PubMed: 38238734
DOI: 10.1186/s12889-024-17685-w -
Orphanet Journal of Rare Diseases Sep 2019Trimethylaminuria (TMAU) is a metabolic disorder characterized by the excessive excretion of the malodorous compound trimethylamine (TMA). The diagnosis of TMAU is...
BACKGROUND
Trimethylaminuria (TMAU) is a metabolic disorder characterized by the excessive excretion of the malodorous compound trimethylamine (TMA). The diagnosis of TMAU is challenging because this disorder is situated at the boundary between biochemistry and psychiatry. Here, we used nuclear magnetic resonance spectroscopy to assess TMAU in 13 patients. We also sequenced the FMO3 gene in 11 of these patients. Treatment with vitamin B2 was prescribed.
RESULTS
Two patients (aged 3 and 9 years at the initial consultation) had a particularly unpleasant body odor, as assessed by their parents and the attending physicians. The presence of high urine TMA levels confirmed the presence of a metabolic disorder. The two (unrelated) children carried compound heterozygous variants in the FMO3 gene. In both cases, vitamin B2 administration decreased TMA excretion and reduced body odor. The 11 adults complained of an unpleasant body odor, but the physicians did not confirm this. In all adult patients, the urine TMA level was within the normal range reported for control (non-affected) subjects, although two of the patients displayed an abnormally high proportion of oxidized TMA. Seven of the 9 tested adult patients had a hypomorphic variant of the FMO3 gene; the variant was found in the homozygous state, in the heterozygous state or combined with another hypomorphic variant. All 11 adults presented a particular psychological or psychiatric phenotype, with a subjective perception of unpleasant odor.
CONCLUSIONS
The results present the clinical and biochemical data of patients complaining of unpleasant body odor. Contrary to adult patients, the two children exhibited all criteria of recessively inherited trimethylaminuria, suspected by parents in infancy. B2 vitamin treatment dramatically improved the unpleasant body odor and the ratio of TMA/Cr vs TMAO/Cr in the urine in the children. Other patients presented a particular psychological or psychiatric phenotype.
Topics: Child; Child, Preschool; Genetic Testing; Humans; Magnetic Resonance Spectroscopy; Metabolism, Inborn Errors; Methylamines; Oxygenases; Phenotype; Riboflavin
PubMed: 31533761
DOI: 10.1186/s13023-019-1174-6 -
JIMD Reports Jan 2021Trimethylaminuria (TMAU) (OMIM #602079) is a rare inherited metabolic condition. TMAU is associated with decreased hepatic trimethylamine N-oxidation, which leads to an...
BACKGROUND
Trimethylaminuria (TMAU) (OMIM #602079) is a rare inherited metabolic condition. TMAU is associated with decreased hepatic trimethylamine N-oxidation, which leads to an excess of the volatile trimethylamine (TMA) instead of substrate conversion to trimethylamine N-oxide (TMAO). TMA is a tertiary amine derived from the enterobacterial metabolism of precursors such as choline and phosphatidylcholine present in the diet, and is also a bacterial metabolite of TMAO, a normal constituent of saltwater fish. When the involved enzyme flavin mono-oxygenase 3 is deficient, TMA builds up and is released in the person's sweat, urine, and breath, giving off a strong body odor. We have recently reported the biochemical and genetic characteristics of 13 Irish adult patients with TMAU attending the main Irish Reference Center. Research on the behavioral and psychosocial aspects of this condition is limited. This study explores the patients' perspectives of living with TMAU in Ireland.
METHODS
A qualitative descriptive phenomenological approach was used. Six adults participated in this study. Data were gathered through semi-structured interviews, which were transcribed and analyzed.
RESULTS
The results suggest that the participants experienced a negative journey to diagnosis. Fear, anxiety, paranoia, and dysfunctional thinking are a constant struggle. Participants reported using avoidant coping mechanisms and strategic planning to navigate daily life.
CONCLUSION
It is considered that the results from this study will inform future interventions with this unique patient cohort.
PubMed: 33473342
DOI: 10.1002/jmd2.12170 -
The Clinical Biochemist. Reviews Feb 2011Trimethylaminuria is a disorder in which the volatile, fish-smelling compound, trimethylamine (TMA) accumulates and is excreted in the urine, but is also found in the...
Trimethylaminuria is a disorder in which the volatile, fish-smelling compound, trimethylamine (TMA) accumulates and is excreted in the urine, but is also found in the sweat and breath of these patients. Because many patients have associated body odours or halitosis, trimethylaminuria sufferers can meet serious difficulties in a social context, leading to other problems such as isolation and depression. TMA is formed by bacteria in the mammalian gut from reduction of compounds such as trimethylamine-N-oxide (TMAO) and choline. Primary trimethylaminuria sufferers have an inherited enzyme deficiency where TMA is not efficiently converted to the non-odorous TMAO in the liver. Secondary causes of trimethylaminuria have been described, sometimes accompanied by genetic variations. 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. 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. Treatment with antibiotics to control bacteria in the gut, or activated charcoal to sequester TMA, may also be beneficial.
PubMed: 21451776
DOI: No ID Found -
Pediatric Gastroenterology, Hepatology... Mar 2022To design a prospective study on endovascular closure of congenital portosystemic shunts. The primary endpoint was to assess the safety of endovascular closure. The...
PURPOSE
To design a prospective study on endovascular closure of congenital portosystemic shunts. The primary endpoint was to assess the safety of endovascular closure. The secondary endpoint was to evaluate the clinical, analytical and imaging outcomes of treatment.
METHODS
Fifteen patients (age range: 2 days to 21 years; 10 male) were referred to our center due to congenital portosystemic shunts. The following data were collected prior to treatment: age, sex, medical history, clinical and analytical data, urine trimethylaminuria, abdominal-US, and body-CT. The following data were collected at the time of intervention: anatomical and hemodynamic characteristics of the shunts, device used, and closure success. The following data were collected at various post-intervention time points: during hospital stay (to confirm shunt closure and detect complications) and at one year after (for clinical, analytical, and imaging purposes).
RESULTS
The treatment was successful in 12 participants, migration of the device was observed in two, while acute splanchnic thrombosis was observed in one. Off-label devices were used in attempting to close the side-to-side shunts, and success was achieved using Amplatzer Ductus-Occluder and Amplatzer Muscular-Vascular-Septal-Defect-Occluder. The main changes were: increased prothrombin activity (=0.043); decreased AST, ALT, GGT, and bilirubin (=0.007, =0.056, =0.036, =0.013); thrombocytopenia resolution (=0.131); expansion of portal veins (=0.005); normalization of Doppler portal flow (100%); regression of liver nodules (=0.001); ammonia normalization (=0.003); and disappearance of trimethylaminuria (=0.285).
CONCLUSION
Endovascular closure is effective. Our results support the indication of endovascular closure for side-to-side shunts and for cases of congenital absence of portal vein.
PubMed: 35360378
DOI: 10.5223/pghn.2022.25.2.147