TY - CHAP
T1 - Transient massive trimethylaminuria associated with food protein–induced enterocolitis syndrome
AU - Miller, Natalie B.
AU - Beigelman, Avraham
AU - Utterson, Elizabeth
AU - Shinawi, Marwan
N1 - Publisher Copyright:
© SSIEM and Springer-Verlag Berlin Heidelberg 2013.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Autosomal recessive disease
KW - Electrospray ionization tandem mass spectrometry
KW - Enzyme capacity
KW - Intestinal permeability
KW - Irritable bowel syndrome
UR - http://www.scopus.com/inward/record.url?scp=84900500630&partnerID=8YFLogxK
U2 - 10.1007/8904_2013_238
DO - 10.1007/8904_2013_238
M3 - Chapter
C2 - 23821320
AN - SCOPUS:84900500630
T3 - JIMD Reports
SP - 11
EP - 15
BT - JIMD Reports
PB - Springer
ER -