caa a22 4500 467932638 CHVBK 20180406152947.0 cr unu---uuuuu 170328e20060201xx s 000 0 eng 10.1007/s10545-006-0158-6 doi (NATIONALLICENCE)springer-10.1007/s10545-006-0158-6 Diagnosis and management of trimethylaminuria (FMO3 deficiency) in children [Elektronische Daten] [R. Chalmers, M. Bain, H. Michelakakis, J. Zschocke, R. Iles] Summary: Persistent trimethylaminuria in children is caused by autosomal recessively inherited impairment of hepatic trimethylamine (TMA) oxidation due to deficiency of flavin monooxygenase 3 (FMO3) secondary to mutations in the FMO3 gene. Trimethylaminuria or ‘fish odour syndrome' is due to excessive excretion into body fluids and breath of TMA derived from the enterobacterial metabolism of dietary precursors. The disorder is present from birth but becomes apparent as foods containing high amounts of choline or of trimethylamine N-oxide (TMAO) from marine (sea or saltwater) fish are introduced into the diet. In our experience, trimethylaminuria (FMO3 deficiency) in children is rare. We have compared the dynamics and diagnostic efficacy of choline loading with marine fish meals in six children with trimethylaminuria. Loading with a marine fish meal provides a simple and acceptable method for confirmation of diagnosis of suspected trimethylaminuria in children, with the effects being cleared more quickly than with a choline load test. However, oral loading with choline bitartrate allows estimation of residual oxidative capacity in vivo and is a useful adjunct to molecular studies. Patients homozygous for the ‘common' P153L mutation in the FMO3 gene showed virtual complete lack of residual TMA N-oxidative capacity, consistent with a nonfunctional or absent FMO3 enzyme, whereas a patient with the M82T mutation showed some residual oxidative capacity. A patient compound heterozygous for two novel mutations, G193E and R483T, showed considerable residual N-oxidative capacity. A further patient, heterozygous for two novel sequence variations in the FMO3 gene, consistently showed malodour and elevated urinary TMA/TMAO ratios under basal conditions but a negative response to both choline and marine fish meal loading. Comparison of the effects of administration of antibiotics (metronidazole, amoxicillin, neomycin) on gut bacterial production of trimethylamine from choline showed they all reduced TMA production to a limited extent, with neomycin being most effective. ‘Best-practice' diagnostic and treatment guidelines are summarized. SSIEM and Springer, 2006 Chalmers R. Paediatric Metabolism Unit, St George's Hospital Medical School, London, UK aut Bain M. Paediatric Metabolism Unit, St George's Hospital Medical School, London, UK aut Michelakakis H. Institute of Child Health, Aghia Sophia Children's Hospital, Athens, Greece aut Zschocke J. Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany aut Iles R. Department of Diabetes and Metabolic Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary College, London, UK aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/1(2006-02-01), 162-172 0141-8955 29:1<162 2006 29 10545 https://doi.org/10.1007/s10545-006-0158-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10545-006-0158-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chalmers R. Paediatric Metabolism Unit, St George's Hospital Medical School, London, UK aut NATIONALLICENCE 700 1- Bain M. Paediatric Metabolism Unit, St George's Hospital Medical School, London, UK aut NATIONALLICENCE 700 1- Michelakakis H. Institute of Child Health, Aghia Sophia Children's Hospital, Athens, Greece aut NATIONALLICENCE 700 1- Zschocke J. Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany aut NATIONALLICENCE 700 1- Iles R. Department of Diabetes and Metabolic Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary College, London, UK aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/1(2006-02-01), 162-172 0141-8955 29:1<162 2006 29 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer