Trimethylaminuria
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Trimethylaminuria (TMAU) is a rare genetic disease that causes a defect in the body's ability to normally produce Flavin containing monooxygenase 3 (FMO3). When FMO3 is compromised, the body loses the ability to properly breakdown trimethylamine. Trimethylamine is consumed through the diet and when not properly broken down, through a process called N-Oxygenation, builds up and is excreted through breath, sweat, and urine.
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[edit] Symptoms
Trimethylamine causes an offensive body odor that resembles rotting fish and is manifested through breath, sweat, and urine. People affected with TMAU may experience psychosocial abnormalities such as depression and social isolation. There also may be additional metabolic problems such as hypertension associated with TMAU.
[edit] Incidence
TMAU is more common among females. The symptoms can worsen around puberty and menopause. There have been transient (temporary) cases reported in women during menstruation, in young children, and in people with copper deficiencies.
[edit] Diagnosis
One of the tests for trimethylaminuria is a urine test for elevated levels of trimethylamine.
A similar test can be used to identify carriers of this condition - those individuals who carry one copy of a mutated gene but do not have symptoms. In this case, the person would be given a high dose of choline (one of the precursors of trimethylamine) and then have their urine tested for elevated levels of trimethylamine.
There also is a DNA test that can detect the genetic defect.
[edit] Treatment
Although there is no cure for trimethylaminuria, it is possible for people with this condition to live relatively normal, healthy lives without the fear of being shunned because of their unpleasant odor. Ways of reducing the odor include:
- Avoiding foods such as eggs, legumes, certain meats, fish, and foods that contain choline, nitrogen, and sulfur.
- Taking low doses of antibiotics to reduce the amount of bacteria in the gut.
- Using soaps with a moderate pH, between 5.5 and 6.5.
- At least one study [1] has suggested that the daily intake of charcoal and/or copper chlorophyllin may be of significant use in improving the quality of life of individuals suffering from TMAU.
Also helpful are:
- Behavioral counseling to help with depression and other psychological symptoms.
- Genetic counseling to better understand their condition.
[edit] Genetics
Most cases of trimethylaminuria appear to be inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene. Carriers may have mild symptoms of trimethylaminuria or experience temporary episodes of fish-like body odor.
Mutations in the FMO3 gene, which is found on the long arm of chromosome 1, cause trimethylaminuria. The FMO3 gene makes an enzyme that breaks down nitrogen-containing compounds from the diet, including trimethylamine. This compound is produced by bacteria in the intestine as they digest proteins from eggs, meat, soy, and other foods. Normally, the FMO3 enzyme converts fishy-smelling trimethylamine into trimethylamine N-oxide which has no odor. If the enzyme is missing or its activity is reduced because of a mutation in the FMO3 gene, trimethylamine is not broken down and instead builds up in the body. As the compound is released in a person's sweat, urine, and breath, it causes the strong odor characteristic of trimethylaminuria. Researchers believe that stress and diet also play a role in triggering symptoms.
There are more than 10 kinds of known mutations associated with TMAU. Loss-of-function mutations, nonsense mutations, and missense mutations are three of the most common. Nonsense and missence mutations cause the most severe phenotypes. Although FMO3 mutations account for most known cases of trimethylaminuria, some cases are caused by other factors. A fish-like body odor could result from an excess of certain proteins in the diet or from an increase in bacteria that normally break down trimethylamine in the digestive system. A few cases of the disorder have been identified in adults with liver damage caused by hepatitis.
[edit] References
- Furnes B, Feng J, Sommer SS, Schlenk D (2003). "Identification of novel variants of the flavin-containing monooxygenase gene family in African Americans". Drug Metab Dispos 31 (2): 187-93. PMID 12527699.
- Hernandez D, Addou S, Lee D, Orengo C, Shephard EA, Phillips IR (2003). "Trimethylaminuria and a human FMO3 mutation database". Hum Mutat 22 (3): 209-13. PMID 12938085.
- Mitchell SC, Smith RL (2001). "Trimethylaminuria: the fish malodor syndrome". Drug Metab Dispos 29 (4 Pt 2): 517-21. PMID 11259343.
- Mitchell SC (1999). "Trimethylaminuria: susceptibility of heterozygotes". Lancet 354 (9196): 2164-5. PMID 10609842.
- Treacy EP, et al. (1998). "Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication". Human Molecular Genetics 7 (5): 839-45.
- Zschocke J, Kohlmueller D, Quak E, Meissner T, Hoffmann GF, Mayatepek E (1999). "Mild trimethylaminuria caused by common variants in FMO3 gene". Lancet 354 (9181): 834-5. PMID 10485731.
This article incorporates public domain text from The U.S. National Library of Medicine and The National Human Genome Research Institute
