Rare Infectious Disease News

Disease Profile

Trimethylaminuria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

TMAU; Fish odor syndrome; Fish malodor syndrome;

Categories

Metabolic disorders

Summary

Trimethylaminuria causes the body to produce a fishy odor that is released in the sweat, urine, breath, and reproductive fluids. People with trimethylaminuria are unable to break down trimethylamine. Trimethylamine comes from specific chemicals (choline, carnitine, TMAO) found in certain foods. The excess trimethylamine builds up and is the source of the odor. There are no other physical symptoms from trimethylaminuria, but people with this condition may experience serious psychological and social distress. Trimethylaminuria is due to a FMO3 gene that is not working correctly. It is inherited in an autosomal recessive pattern. It is diagnosed based on the symptoms, clinical exam, urine analysis, and can be confirmed by genetic testing. Treatment for trimethylaminuria mainly includes diet modification, acidic soaps and lotions, and vitamin B12 supplements. Other treatment options include antibiotics, activated charcoal, and probiotics.[1][2][3][4][5]

Symptoms

Trimethylaminuria causes people to have a rotten fish smell. This odor can be different from person to person. The odor may get worse with activities that increase sweating, such as exercise and emotional stress. In females, symptoms may be worse right before and during menstruation, after taking oral contraceptives, or around the time of menopause. In some people, the odor comes and goes, and in others, it is constant.[1][2]

Trimethylaminuria does not cause any other physical symptoms. However, the odor can interfere with many aspects of daily life, leading to social and psychological problems.[2][3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Anemia
Low number of red blood cells or hemoglobin
0001903
Autosomal recessive inheritance
0000007
Depressivity
Depression
0000716
Hypertension
0000822
Neutropenia
Low blood neutrophil count
Low neutrophil count

[ more ]

0001875
Recurrent pneumonia
0006532
Splenomegaly
Increased spleen size
0001744
Tachycardia
Fast heart rate
Heart racing
Racing heart

[ more ]

0001649
Trimethylaminuria
High urine trimethylamine levels
0003614

Cause

Trimethylaminuria is caused by the FMO3 gene not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1][2]

Diagnosis

Trimethylaminuria is diagnosed based on the symptoms, a clinical exam, and a test to measure the level of trimethylamine in the urine. Genetic testing can also help confirm the diagnosis.[1][2] 

Guidelines for diagnosing trimethylaminuria have been published.[5]

Testing Resources

  • The Biochemical Genetics Laboratory at Children's Hospital Colorado does specialized testing on urine to look for levels of trimethylamine. For information about testing, please contact Lab Client Services at labclientservices@childrenscolorado.org or at 720-777-6711. The lab encourages using the email address instead of calling so they can give you all the materials and information you need. To arrange the test itself, the lab must work directly with your primary care provider (PCP).
  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

Treatment for trimethylaminuria is focused on removing and preventing the bad odor. Options for treatment include diet modification, vitamin B12 (riboflavin) supplements, antibiotic treatment, and probiotics. Other supplements such as activated charcoal can help remove extra trimethylamine from the body. In addition, some people with trimethylaminuria may benefit from behavioral counseling.[2][3]

Specialists involved in the care of someone with trimethylaminuria may include:[1]

  • Nutritionist
  • Medical geneticist
  • Pharmacist
  • Psychologist/psychiatrist

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Social Networking Websites

  • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Trimethylaminuria. This website is maintained by the National Library of Medicine.
  • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Trimethylaminuria. Click on the link to view a sample search on this topic.

References

  1. Phillips I, Shephard E. Primary trimethylaminuria. GeneReviews. Updated Oct 2015; https://www.ncbi.nlm.nih.gov/books/NBK1103/.
  2. Bouchemal N, Ouss L, Brassier A, et al. Diagnosis and phenotypic assessment of trimethylaminuria, and its treatment with riboflavin: H NMR spectroscopy and genetic testing. Orphanet J Rare Dis. 2019; 14(1):222. https://pubmed.ncbi.nlm.nih.gov/31533761.
  3. Schmidt AC, Leroux JC. Treatments of trimethylaminuria: where we are and where we might be heading. Drug Discov Today. Jun, 2020; S1359-6446(20)30254-3. https://pubmed.ncbi.nlm.nih.gov/32615074.
  4. Doyle S, O'Byrne JJ, Nesbitt M, et al. The genetic and biochemical basis of trimethylaminuria in an Irish cohort. JIMD Rep. 2019; 47(1):35-40. https://pubmed.ncbi.nlm.nih.gov/31240165.
  5. Chalmers RA, Bain MD, Michelakakis H, Zschocke J, Iles RA. Diagnosis and management of trimethylaminuria (FMO3 deficiency) in children. J Inherit Metab Dis. Feb 2006; 29(1):162-72. https://pubmed.ncbi.nlm.nih.gov/16601883.

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