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

Background: A 38-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 H-1 NMR spectroscopy to study serum and urine from the pat ient. Results: The concentration of N,N-dimethylglycine (DMG) was increased simil ar to 100-fold in the serum and similar to 20-fold in the urine. The presen ce of DMG as a storage product was confirmed by use of C-13 NMR spectroscop y and gas chromatography-mass spectrometry. The high concentration of DMG w as caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGD H). A homozygous missense mutation was found in the DMGDH gene of the patie nt. Conclusions: DMGDH deficiency must be added to the differential diagnosis o f patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro H-1 NMR spectroscopy of b ody fluids. (C) 1999 American Association for Clinical Chemistry.