Fish odour syndrome.

cholesterolemia and osteoarthritis was treated with atorvastatin 10 mg daily for four months, ending in October 2006. At that time, hypothyroidism was diagnosed, and the atorva statin was temporarily discontinued. She returned to our lipid clinic in September 2009, because her total and low-density-lipoprotein [LDL] cholesterol levels were signi ficantly increased. At this point, rosuva statin 10 mg daily was started. Two weeks after starting the rosuvastatin, the patient noticed a strong fish odour, similar to a problem she had experienced before menopause. When she was nine years old, she had undergone investigation for a strong odour of rotting fish, for which she was ostracized by her classmates. The smell had decreased after puberty, but she still noticed a strong fishy smell around the time of her menstrual periods and when she was eating a choline-rich diet, such as fish and eggs. The smell had disappeared after menopause. At the time when the smell returned, shortly after initiation of rosuvastatin, the patient had been receiving levothyroxine therapy for about three years (since October 2006), and there had been no change in her diet. After two months of rosuvastatin therapy, the smell became intoler able and she stopped taking the drug. Three days later the smell disappeared. Laboratory testing showed that the patient’s liver and kidney functions were all within normal ranges. As would be expected with treatment with a lipid-lowering agent, there had been a decrease in her LDL chol esterol (from 6.9 mmol/L at baseline to 3.2 mmol/L, i.e., a 53.6% reduction). Primary trimethylaminuria (fish odour syndrome) was suspected. Analysis 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 N-oxide to trimethyl amine (92.4:7.6 [normally > 97:3]), as measured by fast atom bombardment mass spectrometry. Subsequent molecular analysis of the coding region of the FMO3 gene (for flavin-containing monooxygenase 3) revealed compound hetero zygosity for one known pathogenic mutation (p.P153L, c.458C>T) and one novel substitution (p.I8T, c.23T>C). The p.I8T substitution is not a known polymorphism for trimethylaminuria, but it may be patho genic. The patient was also hetero zygous for a common variant haplotype (p.[E158K;E308G]) that has been shown to exacerbate excretion of trimethylamine in association with other disease-causing mutations. Pravastatin 20 mg daily was started, and no symptoms were reported after 16 weeks of treatment.