Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Trimethylaminuria

Sometimes called fish odor syndrome.

What is Trimethylaminuria?

• Trimethylaminuria is a rare disorder of metabolism characterized by a defect in the production of the enzyme flavin-containing monooxygenase 3 (FMO3)
  • FMO3 is important for converting trimethylamine into trimethylamine oxide
  • When this process does not occur, trimethylamine accumulates in the body, giving the patient a strong, pungent, fishy odor
• The condition is usually diagnosed with a urine test
  • At times, a urine test can result in a false positive in the presence of certain conditions:
    • Cervical cancer
    • Bacterial vaginosis
    • Severe kidney or liver disease
    • Urinary tract infection
• A blood test can help verify the genetic basis of the disorder
• The condition was first described in 1970

How Do You Get It?

• In most cases, trimethylaminuria is inherited in an autosomal recessive pattern
• The mutation affects the FMO3 gene
  • There are more than 40 mutations linked to the disorder
• Carriers of the mutation may have very mild symptoms or brief episodes of symptoms
• In a very small number of cases, other causes have been identified, such as a diet with an excess of certain proteins, an abnormal increase of bacteria in the digestive tract, metabolic abnormalities, hormonal changes, or hepatitis
• Women are more likely than men to have the disorder

What Are The Symptoms?

• A person living with trimethylaminuria releases trimethylamine in their urine, sweat, breath, and other fluids
• Trimethylamine produces a strong, often fishy body odor
  • In some instances, patients have a strong odor at all times.
  • Most of the time, patients have a noticeable, but more moderate smell that varies over time
• Otherwise people with trimethylaminuria are healthy
• The condition tends to worsen with puberty
• Characteristics of the odor tend vary depending on hormonal changes, amount of sweat, the observer’s own sense of smell, diet, stress levels, and the presence of other odors in the space
• In women, the smell tends to worsen during menstruation, before menstruation, during menopause, and after using oral contraceptives
• The most serious ramifications of the disorder are social and mental
  • Patients often try in vain to cover up the odor
  • Patients may have difficulty maintaining social relationships and avoid contact with others
  • Trimethylaminuria patients are at increased risk of isolation, low self esteem, depression, and suicide

How Is It Treated?

• There is no known cure or treatment for trimethylaminuria
• Some evidence suggests that daily use of copper chlorophyllin and activated charcoal can result in reduction or complete elimination of the odor
• Changes in diet, such as avoiding legumes, fish, red meat, and eggs, can help reduce the odor
• Other measures include using an acidic detergent with a pH between 5.5 and 6.5 and low doses of the antibiotics metronidazole and neomycin, which can reduce the population of gut bacteria

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this condition from the National Organization for Rare Disorders.