what causes urine to smell like rotting fish
CMAJ. 2011 May 17; 183(8): 929–931.
Fish smell syndrome
A 68-year-old woman with familial hyper-cholesterolemia and osteoarthritis was treated with atorvastatin 10 mg daily for iv months, ending in Oct 2006. At that fourth dimension, hypothyroidism was diagnosed, and the atorvastatin was temporarily discontinued. She returned to our lipid clinic in September 2009, because her total and low-density-lipoprotein [LDL] cholesterol levels were significantly increased. At this bespeak, rosuvastatin 10 mg daily was started.
Two weeks afterwards starting the rosuvastatin, the patient noticed a potent fish odour, similar to a problem she had experienced before menopause. When she was nine years old, she had undergone investigation for a strong odor of rotting fish, for which she was ostracized past her classmates. The smell had decreased after puberty, but she nevertheless noticed a strong fishy scent around the time of her menstrual periods and when she was eating a choline-rich diet, such as fish and eggs. The olfactory property had disappeared after menopause.
At the time when the smell returned, shortly after initiation of rosuvastatin, the patient had been receiving levothyroxine therapy for nearly three years (since October 2006), and there had been no alter in her diet. After two months of rosuvastatin therapy, the smell became intolerable and she stopped taking the drug. Three days later the smell disappeared. Laboratory testing showed that the patient'southward liver and kidney functions were all within normal ranges. As would exist expected with treatment with a lipid-lowering agent, there had been a decrease in her LDL cholesterol (from vi.nine mmol/L at baseline to 3.2 mmol/50, i.e., a 53.vi% reduction).
Primary trimethylaminuria (fish odour syndrome) was suspected. Assay of a urine sample obtained after the patient had stopped taking rosuvastatin revealed elevated excretion of trimethylamine and a lower-than-normal percent ratio of trimethylamine North-oxide to trimethylamine (92.4:7.vi [ordinarily > 97:iii]), as measured past fast atom bombardment mass spectrometry.1 Subsequent molecular assay of the coding region of the FMO3 cistron (for flavin-containing monooxygenase 3) revealed chemical compound heterozygosity for ane known pathogenic mutation (p.P153L, c.458C>T) and 1 novel substitution (p.I8T, c.23T>C). The p.I8T substitution is not a known polymorphism for trimethylaminuria, simply information technology may exist pathogenic. The patient was also heterozygous for a common variant haplotype (p.[E158K;E308G]) that has been shown to exacerbate excretion of trimethylamine in clan with other disease-causing mutations.2 Pravastatin 20 mg daily was started, and no symptoms were reported after xvi weeks of treatment.
Give-and-take
Common causes of a fishy odour include poor hygiene, gingivitis, bacterial vaginosis and urinary tract infections. Avant-garde kidney or liver disease may likewise crusade this condition.iii In the patient described hither, a less common crusade was institute. Trimethylaminuria, also known every bit fish odour syndrome, is a metabolic disorder first described in 1970.4 Information technology is characterized by aberrant excretion of trimethylamine in the urine, breath, sweat and vaginal secretions. It may be principal in origin or secondary to liver or kidney damage, or it may be acquired by an increment in the precursors of trimethylamine, such as choline, lecithin or carnitine in the diet.4
The primary syndrome is inherited in an autosomal recessive style. The defective enzyme is flavin-containing monooxygenase three, the cistron for which (FMO3) is located in chromosome region 1q23–25.5 Trimethylamine is derived from the intestinal bacterial degradation of foods rich in choline, lecithin and carnitine. Trimethylamine produced within the intestinal tract is apace absorbed and is converted within the liver, past the action of flavin-containing monooxygenase 3, to trimethylamine North-oxide (Figure 1), which is then excreted in the urine. Affected individuals have a reduced capacity to metabolize trimethylamine into trimethylamine Northward-oxide. Excessive amounts of the volatile molecule are therefore excreted in the torso fluids, which give off a stiff fishy smell.
Schematic presentation of the metabolic pathway of trimethylamine. FMO3 = flavin-containing monooxygenase 3.
Trimethylaminuria was previously considered to be rare, merely evidence suggests that its prevalence is much higher than initially idea. The incidence of heterozygous carriers of the allele for trimethylaminuria has been studied in relatively few populations. The incidence of heterozygous carriers in the white British population has been estimated to be as loftier as 1%,v and the carrier rate may be equally high as 3% in Ecuador and 11% in New Guinea.5 Carriers may have transient episodes or mild symptoms of fish odour syndrome.four
Clues to the diagnosis
The rotten fish odour is usually nowadays from childhood and is exacerbated during puberty. In women, the offensive odour may exist enhanced by oral contraceptives or may increase just before and during menstruation as a result of hormonal inhibition of the oxidation of trimethylamine. Patients with trimethylaminuria have no physical abnormality. However, the unpleasant smell can effect in a multifariousness of psychosocial problems, including withdrawn personality, social isolation, obsessive personal cleansing, disruption of schooling, marital disharmony, clinical depression and suicidal tendencies.6
As mentioned previously, trimethylaminuria should be differentiated from more common causes of a fishy odour, such as poor hygiene, gingivitis, vaginosis, urinary tract infections, and advanced liver and kidney illness.3
The biochemical diagnosis is established by measuring the ratio of trimethylamine N-oxide to trimethylamine in the urine. Among people without trimethylaminuria, more than 97% of excretion occurs as trimethylamine N-oxide. In patients with the condition, the ratio is reduced. To date, several different mutations of the FMO3 gene have been reported to cause fish odour syndrome.5
Handling options
Treatment includes counselling and dietary modifications. An explanation of the biochemical nature of the disorder and the exacerbating factors such as menstruation may help in relieving patients' anxiety. Behavioural counselling may help with depression and other psychological symptoms. Genetic counselling should be considered if the patient has the primary course of the syndrome. Dietary adjustments include avoidance of choline-rich foods, such as egg yolk, liver, kidney, peas, soybeans and body of water fish.3
Expert opinion suggests that a curt course of low-dose neomycin or metronidazole can be used to suppress production of trimethylamine in the gut.7 The use of mildly acidic soaps may help to reduce the smell in some patients.eight Additional therapeutic strategies that may be developed in the future include gene therapy, attempts to colonize the human being gut with microorganisms engineered with human flavin-containing monooxygenase 3 and enzyme induction with drugs.nine
Exacerbation with rosuvastatin
Flavin-containing monooxygenase 3 is known to be involved in the nicotinamide adenine dinucleotide phosphate–dependent oxidation and metabolism of a number of drugs such as tamoxifen, ketoconazole, sulindac sulphide and benzydamine.10 Given this interest, case reports of exacerbation of fish odour syndrome in clan with these drugs and other medications might exist expected, because patients with primary trimethylaminuria may have a reduced ability to metabolize these compounds.
In the patient described here, the symptoms were exacerbated by rosuvastatin. Only ten% of rosuvastatin is metabolized in the liver, and the remainder is excreted unchanged.xi At the moment, nosotros do not know the mechanism or mechanisms by which rosuvastatin exacerbates the symptoms of fish olfactory property syndrome. Rosuvastatin contains a tertiary amine, which is similar in construction to trimethylamine, whereas none of the other statins, such as atorvastatin and pravastatin, have a tertiary amine construction. We hypothesize that rosuvastatin or one of its metabolites interacts with flavin-containing monooxygenase 3, competitively inhibiting the enzyme action and exacerbating the fishy olfactory property. Rosuvastatin may also exacerbate the symptoms of trimethylaminuria through a competitive transport process. It has been shown that drugs that interact with P-glycoprotein (such as rosuvastatin) inhibit the intestinal import of choline.12 This impaired import of choline from the intestine could result in increased bacterial production of trimethylamine in the intestine.
Central points
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Primary trimethylaminuria (fish odour syndrome) is a metabolic disorder that can be exacerbated by flow, specific medications or the intake of choline-rich foods.
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More than mutual causes of a fishy odor include poor hygiene, gingivitis, vaginosis, urinary tract infections, and avant-garde liver and kidney disease.
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Management of trimethylaminuria includes dietary modifications, use of mildly acidic soaps, abstention of certain medications and perchance a short course of neomycin or metronidazole.
Footnotes
Competing interests: None alleged.
This article has been peer reviewed.
Contributors: All of the authors participated equally in writing the article and revising information technology critically for important intellectual content, and all canonical the final version submitted for publication.
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Articles from CMAJ : Canadian Medical Association Periodical are provided here courtesy of Canadian Medical Association
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091902/
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