Guanidinoacetate methyltransferase (GAMT) deficiency diagnosed by proton NMR spectroscopy of body fluids

Udo F.H. Engelke; Maria Tassini; Joseph Hayek; Maaike de Vries; Appie Bilos; Antonio Vivi; Gianni Valensin; Sabrina Buoni; Raffaella Zannolli; Wim Brussel; Berry Kremer; Gajja S. Salomons; Monique J.B.M. Veendrick-Meekes; Leo A.J. Kluijtmans; Éva Morava; Ron A. Wevers

doi:10.1002/nbm.1367

Guanidinoacetate methyltransferase (GAMT) deficiency diagnosed by proton NMR spectroscopy of body fluids

Udo F.H. Engelke, Maria Tassini, Joseph Hayek, Maaike de Vries, Appie Bilos, Antonio Vivi, Gianni Valensin, Sabrina Buoni, Raffaella Zannolli, Wim Brussel, Berry Kremer, Gajja S. Salomons, Monique J.B.M. Veendrick-Meekes, Leo A.J. Kluijtmans, Éva Morava, Ron A. Wevers

Medical Genetics

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

In patients with guanidinoacetate methyltransferase (GAMT) deficiency several parameters may point towards the diagnosis of GAMT deficiency. These include the low levels of creatine and creatinine in urine, the high concentration of guanidinoacetic acid (GAA) in urine and the low levels of creatine and creatinine in the cerebrospinal fluid (CSF). In this study, body fluids from 10 GAMT deficient patients were analysed using 1H NMR spectroscopy. The urine 1D ¹H NMR spectra of all the patients showed a doublet resonance at 3.98 ppm (pH 2.50) derived from GAA present in high concentration. For this compound, a good recovery and good correlation was found between an LC-MS/MS method and ¹H NMR spectroscopy. In CSF NMR spectra of these patients, the singlet resonances of creatine and creatinine (3.05 and 3.13 ppm, respectively) were absent (normally always present in ¹H NMR spectra of CSF). Due to overlap by other resonances, the doublet of GAA could not be observed. Our data demonstrate that ¹H NMR spectroscopy of urine and CSF can be used to diagnose patients with GAMT deficiency.

Original language	English (US)
Pages (from-to)	538-544
Number of pages	7
Journal	NMR in Biomedicine
Volume	22
Issue number	5
DOIs	https://doi.org/10.1002/nbm.1367
State	Published - 2009

Keywords

Creatine
Creatine biosynthesis
Creatinine
Guanidino-acetic acid
Guanidinoacetate methyltransferase
In vitro H NMR spectroscopy
L-arginine:glycine amidinotransferase

ASJC Scopus subject areas

Molecular Medicine
Radiology Nuclear Medicine and imaging
Spectroscopy

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Engelke, U. F. H., Tassini, M., Hayek, J., de Vries, M., Bilos, A., Vivi, A., Valensin, G., Buoni, S., Zannolli, R., Brussel, W., Kremer, B., Salomons, G. S., Veendrick-Meekes, M. J. B. M., Kluijtmans, L. A. J., Morava, É., & Wevers, R. A. (2009). Guanidinoacetate methyltransferase (GAMT) deficiency diagnosed by proton NMR spectroscopy of body fluids. NMR in Biomedicine, 22(5), 538-544. https://doi.org/10.1002/nbm.1367

Engelke, UFH, Tassini, M, Hayek, J, de Vries, M, Bilos, A, Vivi, A, Valensin, G, Buoni, S, Zannolli, R, Brussel, W, Kremer, B, Salomons, GS, Veendrick-Meekes, MJBM, Kluijtmans, LAJ, Morava, É & Wevers, RA 2009, 'Guanidinoacetate methyltransferase (GAMT) deficiency diagnosed by proton NMR spectroscopy of body fluids', NMR in Biomedicine, vol. 22, no. 5, pp. 538-544. https://doi.org/10.1002/nbm.1367

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abstract = "In patients with guanidinoacetate methyltransferase (GAMT) deficiency several parameters may point towards the diagnosis of GAMT deficiency. These include the low levels of creatine and creatinine in urine, the high concentration of guanidinoacetic acid (GAA) in urine and the low levels of creatine and creatinine in the cerebrospinal fluid (CSF). In this study, body fluids from 10 GAMT deficient patients were analysed using 1H NMR spectroscopy. The urine 1D 1H NMR spectra of all the patients showed a doublet resonance at 3.98 ppm (pH 2.50) derived from GAA present in high concentration. For this compound, a good recovery and good correlation was found between an LC-MS/MS method and 1H NMR spectroscopy. In CSF NMR spectra of these patients, the singlet resonances of creatine and creatinine (3.05 and 3.13 ppm, respectively) were absent (normally always present in 1H NMR spectra of CSF). Due to overlap by other resonances, the doublet of GAA could not be observed. Our data demonstrate that 1H NMR spectroscopy of urine and CSF can be used to diagnose patients with GAMT deficiency.",

keywords = "Creatine, Creatine biosynthesis, Creatinine, Guanidino-acetic acid, Guanidinoacetate methyltransferase, In vitro H NMR spectroscopy, L-arginine:glycine amidinotransferase",

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AU - Engelke, Udo F.H.

AU - Tassini, Maria

AU - Hayek, Joseph

AU - de Vries, Maaike

AU - Bilos, Appie

AU - Vivi, Antonio

AU - Valensin, Gianni

AU - Buoni, Sabrina

AU - Zannolli, Raffaella

AU - Brussel, Wim

AU - Kremer, Berry

AU - Salomons, Gajja S.

AU - Veendrick-Meekes, Monique J.B.M.

AU - Kluijtmans, Leo A.J.

AU - Morava, Éva

AU - Wevers, Ron A.

PY - 2009

Y1 - 2009

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AB - In patients with guanidinoacetate methyltransferase (GAMT) deficiency several parameters may point towards the diagnosis of GAMT deficiency. These include the low levels of creatine and creatinine in urine, the high concentration of guanidinoacetic acid (GAA) in urine and the low levels of creatine and creatinine in the cerebrospinal fluid (CSF). In this study, body fluids from 10 GAMT deficient patients were analysed using 1H NMR spectroscopy. The urine 1D 1H NMR spectra of all the patients showed a doublet resonance at 3.98 ppm (pH 2.50) derived from GAA present in high concentration. For this compound, a good recovery and good correlation was found between an LC-MS/MS method and 1H NMR spectroscopy. In CSF NMR spectra of these patients, the singlet resonances of creatine and creatinine (3.05 and 3.13 ppm, respectively) were absent (normally always present in 1H NMR spectra of CSF). Due to overlap by other resonances, the doublet of GAA could not be observed. Our data demonstrate that 1H NMR spectroscopy of urine and CSF can be used to diagnose patients with GAMT deficiency.

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KW - Creatine biosynthesis

KW - Creatinine

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KW - Guanidinoacetate methyltransferase

KW - In vitro H NMR spectroscopy

KW - L-arginine:glycine amidinotransferase

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Guanidinoacetate methyltransferase (GAMT) deficiency diagnosed by proton NMR spectroscopy of body fluids

Abstract

Keywords

ASJC Scopus subject areas

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