Diagnosis and management of trimethylaminuria (FMO3 deficiency) in children.

摘要: Persistent trimethylaminuria in children is caused by autosomal recessively inherited impairment of hepatic trimethylamine (TMA) oxidation due to deficiency flavin monooxygenase 3 (FMO3) secondary mutations the FMO3 gene. Trimethylaminuria or 'fish odour syndrome' excessive excretion into body fluids and breath TMA derived from enterobacterial metabolism dietary precursors. The disorder present birth but becomes apparent as foods containing high amounts choline N-oxide (TMAO) marine (sea saltwater) fish are introduced diet. In our experience, (FMO3 deficiency) rare. We have compared dynamics diagnostic efficacy loading with meals six trimethylaminuria. Loading a meal provides simple acceptable method for confirmation diagnosis suspected children, effects being cleared more quickly than load test. However, oral bitartrate allows estimation residual oxidative capacity vivo useful adjunct molecular studies. Patients homozygous 'common' P153L mutation gene showed virtual complete lack N-oxidative capacity, consistent nonfunctional absent enzyme, whereas patient M82T some capacity. A compound heterozygous two novel mutations, G193E R483T, considerable further patient, sequence variations gene, consistently malodour elevated urinary TMA/TMAO ratios under basal conditions negative response both loading. Comparison administration antibiotics (metronidazole, amoxicillin, neomycin) on gut bacterial production they all reduced limited extent, neomycin most effective. 'Best-practice' treatment guidelines summarized.