Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

A compound heterozygous mutation in the FMO3 gene: the first pediatric case causes fish odor syndrome in Korea

  • Kim, Ji Hyun (Department of Pediatrics, Dongguk University Ilsan Hospital) ;
  • Cho, Sung Min (Department of Pediatrics, Dongguk University Ilsan Hospital) ;
  • Chae, Jong-Hee (Department of Pediatrics, Seoul National University College of Medicine)
  • Received : 2016.08.05
  • Accepted : 2017.02.16
  • Published : 2017.03.15
Download PDF
⟨ Previous Next ⟩

Abstract

Trimethylaminuria (TMAuria), known as "fish odor syndrome," is a congenital metabolic disorder characterized by an odor resembling that of rotting fish. This odor is caused by the secretion of trimethylamine (TMA) in the breath, sweat, and body secretions and the excretion of TMA along with urine. TMAuria is an autosomal recessive disorder caused by mutations in flavin-containing monooxygenase 3 (FMO3). Most TMAuria cases are caused by missense mutations, but nonsense mutations have also been reported in these cases. Here, we describe the identification of a novel FMO3 gene mutation in a patient with TMAuria and her family. A 3-year-old girl presented with a strong corporal odor after ingesting fish. Genomic DNA sequence analysis revealed that she had compound heterozygous FMO3 mutations; One mutation was the missense mutation p.Val158Ile in exon 3, and the other was a novel nonsense mutation, p.Ser364X, in exon 7 of the FMO3 gene. Familial genetic analyses showed that the p.Val158Ile mutation was derived from the same allele in the father, and the p.Ser364X mutation was derived from the mother. This is the first description of the p.Ser364X mutation, and the first report of a Korean patient with TMAuria caused by novel compound heterozygous mutations.

Keywords

References

  1. Ayesh R, Mitchell SC, Zhang A, Smith RL. The fish odour syndrome: biochemical, familial, and clinical aspects. BMJ 1993;307: 655-7. https://doi.org/10.1136/bmj.307.6905.655
  2. van Thriel C, Schaper M, Kiesswetter E, Kleinbeck S, Juran S, Blaszkewicz M, et al. From chemosensory thresholds to whole body exposures-experimental approaches evaluating chemosensory effects of chemicals. Int Arch Occup Environ Health 2006;79: 308-21. https://doi.org/10.1007/s00420-005-0057-4
  3. Motika MS, Zhang J, Cashman JR. Flavin-containing monooxygenase 3 and human disease. Expert Opin Drug Metab Toxicol 2007;3:831-45. https://doi.org/10.1517/17425255.3.6.831
  4. Chalmers RA, Bain MD, Michelakakis H, Zschocke J, Iles RA. Diagnosis and management of trimethylaminuria (FMO3 deficiency) in children. J Inherit Metab Dis 2006;29:162-72. https://doi.org/10.1007/s10545-006-0158-6
  5. Yamazaki H, Shimizu M. Survey of variants of human flavin-containing monooxygenase 3 (FMO3) and their drug oxidation activities. Biochem Pharmacol 2013;85:1588-93. https://doi.org/10.1016/j.bcp.2013.03.020
  6. Yi HG, Lee JN, Ryu SD, Kang JH, Cha YN, Park CS. Secondary fish-odor syndrome can be acquired by nitric oxide-mediated impairment of flavin-containing monooxygenase in hepatitis B virus-infected patients. Korean J Physiol Pharmacol 2004;8:213-8.
  7. Cashman JR, Zhang J. Human flavin-containing monooxygenases. Annu Rev Pharmacol Toxicol 2006;46:65-100. https://doi.org/10.1146/annurev.pharmtox.46.120604.141043
  8. Hernandez D, Addou S, Lee D, Orengo C, Shephard EA, Phillips IR. Trimethylaminuria and a human FMO3 mutation database. Hum Mutat 2003;22:209-13. https://doi.org/10.1002/humu.10252
  9. Shimizu M, Allerston CK, Shephard EA, Yamazaki H, Phillips IR. Relationships between flavin-containing mono-oxygenase 3 (FMO3) genotype and trimethylaminuria phenotype in a Japanese population. Br J Clin Pharmacol 2014;77:839-51. https://doi.org/10.1111/bcp.12240
  10. Christodoulou J. Trimethylaminuria: an under-recognised and socially debilitating metabolic disorder. J Paediatr Child Health 2012;48:E153-5. https://doi.org/10.1111/j.1440-1754.2010.01978.x
  11. Mountain H, Brisbane JM, Hooper AJ, Burnett JR, Goldblatt J. Trimethylaminuria (fish malodour syndrome): a "benign" genetic condition with major psychosocial sequelae. Med J Aust 2008;189: 468.
  12. Mitchell SC, Smith RL. Trimethylaminuria: the fish malodor syndrome. Drug Metab Dispos 2001;29(4 Pt 2):517-21.
  13. Phillips IR, Shephard EA. Primary trimethylaminuria. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(R). Seattle (WA): University of Washington, Seattle. 1993-2017.
  14. Messenger J, Clark S, Massick S, Bechtel M. A review of trimethylaminuria: (fish odor syndrome). J Clin Aesthet Dermatol 2013;6: 45-8.
  15. Manning NJ, Allen EK, Kirk RJ, Sharrard MJ, Smith EJ. Riboflavin-responsive trimethylaminuria in a patient with homocystinuria on betaine therapy. JIMD Rep 2012;5:71-5.

Cited by

  1. Acrolein‐induced atherogenesis by stimulation of hepatic flavin containing monooxygenase 3 and a protection from hydroxytyrosol vol.234, pp.1, 2017, https://doi.org/10.1002/jcp.26600
  2. Development and feasibility of the use of an assessment tool measuring treatment efficacy in patients with trimethylaminuria: A mixed methods study vol.42, pp.2, 2017, https://doi.org/10.1002/jimd.12023
  3. A series of simple detection systems for genetic variants of flavin-containing monooxygenase 3 (FMO3) with impaired function in Japanese subjects vol.41, pp.None, 2017, https://doi.org/10.1016/j.dmpk.2021.100420