Occasionally, rarely, in clinical practice one encounters a patient who has a persistent fish odor. Apparently William Shakespeare encountered such a person, for in “The Tempest” he writes "What have we here? A man or a fish? Dead or alive? He smells like a fish; a very ancient and fish-like smell . . ." Shakespeare's description of the socially rejected island dweller, Caliban, aptly demonstrates that people have long been aware of a particularly offensive smell. Some people have a mild fish-like odor and others have a strong, extremely offensive such odor. These people have a rare genetic disorder known as Fish Odor Syndrome. They have an odor no amount of bathing or perfuming will disappear. Although only about a hundred cases have been described in the scientific literature worldwide, the syndrome may not be as rare as that number suggests. Trimethylaminuria is only occasionally identified during childhood. Some cases of trimethylaminuria may have no genetic component: Several patients seem to have developed the disorder after liver or kidney disease. Few health professionals are aware of this disease, which is called trimethylaminuria, people experiencing its characteristic body odor may spend years seeking relief. They often acquire a long list of inaccurate diagnoses, ranging from poor hygiene to psychiatric problems. These people may withdraw from the outside world to avoid ridicule or try to mask their odor with strong perfumes and cigarettes. Many of those with the disorder also report symptoms of depression. This syndrome can be highly destructive to a person's personal and social life as well as to work and career. source:http://www.medical-library.net/content/view/217/41/ We believe that these people fail to metabolized trimethylaminuria and that this is the source of the fishy smell. It is an enzyme deficiency produced by a genetically inherited condition. The first case of trimethylaminuria was described in the medical literature in the 1970s, but literary references may go back a thousand years. For example, an ancient Hindu tale describes a maiden who "grew to be comely and fair, but a fishy odor ever clung to her." Although they show no apparent lack of hygiene or obvious medical symptoms, most people with the disorder report having foul body odors, bad breath, or a bad taste in their mouths. Studies in the last few years have shown that trimethylaminuria results from defects in an enzyme that breaks down trimethylamine, a byproduct of protein digestion released by bacteria living in the gut. This small molecule — the compound that gives fish their fishy odor — smells foul or garbage-like at low concentrations and fishy in larger amounts. People with the disorder can release trimethylamine through breath, sweat, and urine. A few have a strong odor all the time, but most others experience a less severe smell that fluctuates over time. Researchers speculate that the variability of symptoms indicates that a range of genetic mutations can cause the disease and that stress and diet play a role in triggering symptoms. There is no cure for fish odor syndrome, but a special diet can alleviate the worst of the odor problems. This low-protein regime restricts the amino acid choline, a building block of protein naturally found in high concentrations in fish, eggs, beans, and organ meats. Some people also report that limiting lecithin, a common food additive that is also naturally found in eggs, soybeans, and corn, helps reduce odor. Because bacteria in the gut produce most of the trimethylamine in the body, some people have found that low doses of antibiotics, which kill off these bacteria, temporarily help keep odor down. Odor problems are such a sensitive topic that many people may be wary of talking about their symptoms to a doctor, says Harry W. McConnell of King's College Hospital in London. "The name [fish odor syndrome] contributes greatly to the stigma of this disorder," he says, adding that the name "is misleading since the odor is variable." Because the disease is practically unknown by any name, it may take years for a person with trimethylaminuria to find a doctor who can recognize the problem. In a survey given to 22 people who had been identified as having the syndrome, McConnell found that it typically took them 5 to 10 years to seek medical care after their symptoms appeared. The correct diagnosis then required, on average, another 10 years. We do not know why the syndrome seems to be more common in women than in men. Perhaps sex hormones exacerbate symptoms. A variety of reports say that the disease in women gets worse around puberty, just before and during menstrual periods, after taking oral contraceptives, and around menopause. Scientists discovered the gene implicated in trimethylaminuria in 1997. Located on the end of a chromosome, it encodes one of a series of enzymes called flavin monooxygenases (FMOs). Researchers suspect that these enzymes' most important role is in eliminating environmental toxins from the body. The enzyme known as FMO3, for example, helps break down diet-derived nitrogen-containing compounds, including trimethylamine, and possibly drugs containing nitrogen, sulfur, and phosphorus. The gene for FMO3 can suffer from any of about 10 different mutations. Most people showing symptoms of trimethylaminuria have inherited two mutated copies of the gene. Scientists suggest that the variety of genetic mutations might explain differences in the timing of disease onset and how strong the odor is. Environmental factors may also play a role. Some types of bacteria that people have in their guts might produce more trimethylaminuria than other types. Animal studies have provided evidence that a compound known as indole-3-carbinol, found in broccoli and other dark green vegetables, blocks the function of the enzyme system that breaks down trimethylamine. Avoiding broccoli and other leafy greens, in addition to limiting protein intake, might help reduce odor problems. Because FMO3's functions in the body are not well understood, doctors don't know what symptoms, other than odor, might be linked to trimethylaminuria. Researchers suspect that the enzyme breaks down many substances besides trimethylamine. For example, various drugs, such as antidepressants, may be broken down by FMO3. If the enzyme isn't working properly, people might suffer additional side effects from some of these drugs, they suggest. The liver, a reservoir of digestive enzymes, produces most of the body's FMOs. Production of these proteins has also been detected in midbrain nerve cells, skeletal muscle, adrenal and salivary glands, thyroid and lung tissue, and the skin. The functions of the enzymes in these various locations remain unknown. Although the vast majority of people so far diagnosed with the disorder appear to have normal mental and physical abilities, some researchers suspect that the enzyme deficiency itself may cause depression and trigger seizures. Challenge tests for trimethylaminuria in England indicate that up to 1 percent of people worldwide carry at least one copy of a mutated gene for the critical enzyme, McConnell reports. 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. Researchers believe that equatorial regions have even higher percentages of people carrying the mutated genes, McConnell says.