Trimethylaminuria was first discovered in 1970 by J.R. Humbert. It was found in a six-year-old girl with multiple pulmonary infections. A deficiency of trimethylamine-oxidase was shown in a liver biopsy. The mutated gene, which is responsible for the disease, was only recently identified by C.T. Dolphin in 1997 as the gene that codes for the enzyme flavin monooxygenase 3. In a normal person, dietary choline and trimethylamine-oxide are ingested and broken down by bacteria in the intestines, producing trimethylamine. This is then absorbed and transported to the liver. It is oxidized in the liver by FMO3 to trimethylamine-N-oxide, which is odorless. It is then excreted in the urine. In a person with TMA, there is a diminishing FMO3 activity, resulting in the loss of oxidation of trimethylamine. There becomes an accumulation and massive excretion of trimethylamine in the urine and from areas of active sweating. Unoxidized trimethylamine causes the fishy odor of the TMA. Odor problems are such a sensitive topic that many people are wary of talking to a doctor about their symptoms. ?The name [fish odor syndrome] contributes greatly to the stigma of this disorder. It is misleading since the odor is variable?(Harry W. McConnell).
Because trimethylaminuria is so unknown, it takes suffers years to find out what is wrong, and then even more years to find someone who knows how to properly treat them. Since so little is known by doctors and researchers about this disease, it makes it very hard to treat. Also, the patient’s reaction to the types of treatment varies, so there is no real cure for the disease. Trimethylaminuria is only occasionally identified during childhood. ?The affected children, however, are likely to become disturbed and even suicidal because of the problems their odor causes in schools.? (Ertan Mayatepek).
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The odor problems in children seem to disappear as they get older. The syndrome seems to occur more in women and researchers suspect that it has to do with sex hormones. Some cases have no genetic component: Several patients can develop the disorder after kidney or liver disease. Some studies have suggested that people who carry only one copy of a mutated gene may be susceptible to transient fish-odor attacks during periods of stress or after eating foods that contain large amounts of trimethylamine or its chemical precursors (Stephen C. Mitchell).
Challenge tests for trimethylaminuria in England indicate that up to one percent of people worldwide carry at least one copy of a mutated gene for the critical enzyme (Harry W. McConnell).
Because people must inherit two copies of a mutated gene to show symptoms of the disease, 1 in 10,000 people would be expected to have the syndrome (Christensen, 317).
Researchers believe that equatorial regions have even higher percentages of people carrying the mutated genes (Harry W. McConnell).
If mutations in the FMO3 gene are as common as scientists suspect, it might be worth developing a screening test to be used at birth (Eileen Treacy).
Treatment starts with an alteration of diet. All foods that contain trimethylamine or choline should be eliminated from your daily intake. Foods that contain these ingredients are eggs, liver, legumes, some grains, some saltwater fish, and many more. For most this change in diet helps with the smell, but for others it goes beyond the diet. Antibiotics are also used to reduce the bacterial load of the gut. People diagnosed with TMA may also suffer from severe hypertension and tachycardia after eating foods containing tyramine (FMO3 also metabolizes tyramine).
In addition, there are several other conditions associated with TMA such as dermatological problems and a wide range of neurological symptoms. TMA has also been seen in patients suffering from Noonan?s, Turner?s, and Prader-Willi syndromes. Researchers suspect that the enzyme breaks down many substances besides trimethylaminuria (Christensen, 317).
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It has been thought to break down certain drugs such as antidepressants. Since trimethylaminuria causes mental anguish and depression, many patients are on these types of drugs. A few people with the disease reported that they had taken antidepressants, but the drugs did not seem effective and actually worsened their odor (Christensen 317).
People that have this dreaded and unheard of disease aren’t really looking for a cure any more. Their major concern is that they want answers to their questions and information about their disorder. “The ignorance and confusion surrounding trimethylaminuria are perhaps the most devastating parts of the disease. It’s absolutely essential to get the word out. We have a potentially treatable disorder that is grossly underdiagnosed” (Harry W. McConnell).
