Transient Massive Trimethylaminuria Associated with Food Protein–Induced Enterocolitis Syndrome
Trimethylaminuria (TMAU) is an autosomal recessive disease caused by excessive excretion into body fluids and breath of unoxidized trimethylamine (TMA) derived from the enterobacterial metabolism of dietary precursors. The condition is caused by deficiency of flavin-containing monooxygenase 3 (FMO3) which leads to impairment of hepatic TMA oxidation to the odorless trimethylamine N-oxide. Secondary TMAU is due to substrate overload in individuals with genetically determined reduced enzyme activity. Food protein–induced enterocolitis syndrome (FPIES) is characterized by recurrent episodes of emesis, diarrhea, dehydration, and lethargy after ingestion of offending foods. Its pathophysiology involves local non-IgE-mediated inflammation of the gastrointestinal tract, which leads to increased intestinal permeability. We report on an 8-month-old male who presented with typical episodes of FPIES associated with intense fish-like body odor. Further investigation in our patient revealed massive urinary TMA excretion during acute FPIES presentation and complete normalization between these episodes. The patient was found to be heterozygous for a novel, paternally inherited nonsense p.Tyr331X mutation and for two maternally inherited common polymorphisms, E158K and E308G, in the FMO3 gene. We propose that our patient was able to cope with the daily burden of TMA, but when challenged with substrate overload, he failed to oxidize TMA due to limited reserve enzyme capacity. We discuss the pathophysiology of TMAU and FPIES and suggest potential mechanisms for the clinical and biochemical findings. Our report illustrates the complex interplay of genetic and environmental factors in TMAU and sheds light on the pathophysiology of FPIES.
KeywordsIrritable Bowel Syndrome Intestinal Permeability Autosomal Recessive Disease Electrospray Ionization Tandem Mass Spectrometry Enzyme Capacity
- Chung HL, Hwang JB, Park JJ, Kim SG (2002) Expression of transforming growth factor b1, transforming growth factor type I and II receptors, and TNF-a in the mucosa of the small intestine in infants with food protein-induced enterocolitis syndrome. J Allergy Clin Immunol 109(1):150–154PubMedCrossRefGoogle Scholar
- Phillips IR, Shephard EA [2007 Oct 8 (Updated 2011 Apr 19)]. Trimethylaminuria. In: Pagon RA, Bird TD, Dolan CR, et al (eds) GeneReviews™ [Internet]. University of Washington, Seattle (WA); Seattle, 1993–. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1103/
- US Database for the Choline Content of Common Foods, 2008. http://www.nal.usda.gov/fnic/foodcomp/Data/Choline/Choln02.pdf. Accessed 5/11/12