Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: NMR spectroscopy study

Clin Chem. 1999 Apr;45(4):459-64.

Abstract

Background: A38-year-old man presented with a history of fish odor (since age 5) and unusual muscle fatigue with increased serum creatine kinase. Our aim was to identify the metabolic error in this new condition.

Methods: We used 1H NMR spectroscopy to study serum and urine from the patient.

Results: The concentration of N, N-dimethylglycine (DMG) was increased approximately 100-fold in the serum and approximately 20-fold in the urine. The presence of DMG as a storage product was confirmed by use of 13C NMR spectroscopy and gas chromatography-mass spectrometry. The high concentration of DMG was caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGDH). A homozygous missense mutation was found in the DMGDH gene of the patient.

Conclusions: DMGDH deficiency must be added to the differential diagnosis of patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro 1H NMR spectroscopy of body fluids.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dimethylglycine Dehydrogenase
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolism, Inborn Errors / blood
  • Metabolism, Inborn Errors / enzymology*
  • Metabolism, Inborn Errors / physiopathology
  • Metabolism, Inborn Errors / urine
  • Mitochondrial Proteins
  • Mutation, Missense
  • Odorants
  • Oxidoreductases, N-Demethylating / deficiency
  • Oxidoreductases, N-Demethylating / genetics*
  • Oxidoreductases, N-Demethylating / urine
  • Sarcosine / analogs & derivatives
  • Sarcosine / urine

Substances

  • Mitochondrial Proteins
  • dimethylglycine
  • Oxidoreductases, N-Demethylating
  • DMGDH protein, human
  • Dimethylglycine Dehydrogenase
  • Dmgdh protein, mouse
  • Sarcosine