Citations 2
Defect in Dimethylglycine Dehydrogenase, a New Inborn Error of Metabolism: NMR Spectroscopy Study
Moolenaar, Sytske H., Poggi-Bach, Jo, Engelke, Udo F. H. , Corstiaensen, Jacqueline MB, Jong, Jan GN de, Binzak, Barbara A., Heerschap, Arend , Jong, Jan G.N. de, Vockley, Jerry , Wevers, Ron A.
Clinical Chemistry | January 23, 2020 | Volume: 45 | Issue: 4 | Pages: 459-464
AbstractBackground: 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 ∼100-fold in the serum and ∼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.
Methodological consensus on clinical proton MRS of the brain: Review and recommendations
Wilson, Martin , Andronesi, Ovidiu C. , Barker, Peter B. , Bartha, Robert , Bizzi, Alberto , Bolan, Patrick J. , Cudalbu, Cristina , Dydak, Ulrike , Emir, Uzay E. , González, R. Gilberto , Gruber, Stephan , Gupta, Rakesh K. , Henning, A , Hetherington, Hoby P. , Hüppi, Petra S. , Hurd, Ralph E. , Kantarci, Kejal , Kauppinen, Risto A. , Klomp, Dennis W. J. , Kreis, Roland , Kruiskamp, Marijn J., Leach, Martin O. , Lin, Alexander , Luijten, Peter R. , Marjańska, Małgorzata , Meyerhoff, Dieter J. , Mountford, Carolyn E. , Mullins, Paul G. , Murdoch, James B. , Nelson, Sarah J. , Noeske, Ralph , Öz, Gülin , Pan, Julie W., Poptani, Harish , Posse, Stefan , Ratai, Eva‐Maria , Salibi, Nouha , Scheenen, Tom W. J. , Soher, Brian J. , Tkáč, Ivan , Vigneron, Daniel B. , Howe, Franklyn A. , Choi, In‐Young , Kreis, Roland , Maudsley, Andrew A , Howe, Franklyn A , Öz, Gülin , Marjańska, Małgorzata , Kantarci, Kejal , Brindle, Kevin Michael , Choi, In‐Young, Gruetter, Rolf , Heerschap, Arend , Peet, Andrew C. , Smith, Ian C. P.
Magnetic Resonance in Medicine | March 28, 2019 | Volume: 82 | Issue: 2 | Pages: 527-550
Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good‐quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi‐adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.