Trimethylaminuria

__**Trimethylaminuria **__


 * Root Cause: **

It is a rare metabolic disorder that is formed by bacteria in the mammalian gut which is caused by reduction of compounds like Trimethylamin-N-oxide (TMAO) and choline.[1] Trimethylamine is derived from the intestinal bacterial degradation of foods which are choline and carnitine rich.[2] Primary causes are due to inherited enzyme deficiency which is when trimethylamine (TMA) is not able to convert into odorless trimethylamine-N-oxide (TMAO) in the liver. This produces accumulation of TMA. Secondary causes are caused by a variety of genetic variations.[1] Uremia can cause more or less unpleasant odor. Poor uremic control can also worsen the odor.[2]


 *  Affected Cell Types: **

The critical enzyme involved in this disorder is a hepatic microsomal flavin-containing monooxygenase called FMO3which is located on chromosome 1 at position 24.3. This virus infects the FMO3 gene, which provides instruction to make an enzyme to break down nitrogen containing compounds including trimethylamine.[1]



 Historical Background:

In The Lancet of the 19th century, there were 2 cases involved in this fishy smelling body odor but cannot be proven they are the same disease. The first clinical case known was obtained in 1970 by a 6 year old who had an unrelated immunodeficiency disorder as well as a marked fishy smelling breath. This was documented as unmetabolized TMA in urine and body secretions like sweat glands. The rate of the disorder is unknown, but there are still more than 200 cases described. The disease went from rare to uncommon. [1]


 *  Common Symptoms: **

Accumulation of TMA produces symptoms of a volatile fishy smell that is excreted through the urine, sweat, and breath of trimethylaminuria patients. Since the odor can cause difficulties in social relationships, the disorder also correlates with isolation and depression.[1] To Diagnose trimethylaminuria, one must analyze total percentage of trimethylamine (free TMA as well as the odorless metabolite TMAO) excreted in the urine as unmetabolized TMA. But if a patient is anuric, these tests can’t be performed.[2]


 *  Standard Treatment: **

There are no current cures or effective treatments.[1] L-Carnitene treatment was used in the past but is not being used anymore.[2] But it is reduced by avoiding certain foods, low doses of antibodies like neomycin, and taking laxatives. Certain foods containing TMAO, like marine fish,[1] as well as choline and lecithin should be avoided to avoid precursors. Symptoms can be decreased significantly when using a home dialysis program.[2] Laxatives can decrease the transit time which can decrease the amount of trimethylamine produced in the gut.[1]


 * Current Research: **

MacKay, R.J. (2011). “Trimethylaminuria: Causes and Diagnosis of Socially Distressing Condition.” Clin Biochem Rev. 31: 33-43.

Hur, E. et. al. (2012). “Trimethylaminuria (fish malodour syndrome) in chronic renal failure.” Hippokratia. 16(1): 83-85.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Pellicciari, A. et. al. (2011). “Epilepsy and trimethylaminuria: A new case report and literature review.” Brain & Development. 33(7): 593-596.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Wise, P.M. et. al. (2011). “Individuals Reporting Idiopathic Malodor Production: Demographics and Incidence of Trimethylaminuria.” American Journal of Medicine. 124(11): 1058-1063.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Christodoulou, J. (2012) “Trimethylaminuria: An under-recognised and socially debilitating metabolic disorder.” Journal of Paediatrics & Child Health. 48(3): E153-E155.


 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;"> References: **

<span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">MacKay, R.J. et. al. (2011). “Trimethylaminuria: Causes and Diagnosis of Socially Distressing Condition.” Clin Biochem Rev. 31: 33-43.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Hur, E. et. al. (2012). “Trimethylaminuria (fish malodour syndrome) in chronic renal failure.” Hippokratia. 16(1): 83-85.