Laboratory Diagnosis of Cerebral Creatine Deficiency Syndromes by Determining Creatine and Guanidinoacetate in Plasma and Urine

Ning Liu; Qin Sun

doi:10.1007/978-1-0716-2565-1_12

Laboratory Diagnosis of Cerebral Creatine Deficiency Syndromes by Determining Creatine and Guanidinoacetate in Plasma and Urine

Methods Mol Biol. 2022:2546:129-140. doi: 10.1007/978-1-0716-2565-1_12.

Authors

Ning Liu^{1

2}, Qin Sun^{3

4}

Affiliations

¹ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
² Baylor Genetics, Houston, TX, USA.
³ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. [email protected].
⁴ Baylor Genetics, Houston, TX, USA. [email protected].

PMID: 36127584
DOI: 10.1007/978-1-0716-2565-1_12

Abstract

Cerebral creatine deficiency syndromes are caused by the dysfunctional creatine biosynthesis or transport and comprise three hereditary neurodevelopmental defects including arginine-glycine amidinotransferase (AGAT), guanidinoacetate methyltransferase (GAMT), and creatine transporter deficiencies. All conditions are characterized by seizures, intellectual disability, and behavioral abnormalities. Laboratory diagnosis of these disorders relies on the determination of creatine and guanidinoacetate concentrations in both plasma and urine. Here we describe a rapid quantitative UPLC/MS/MS method for the simultaneous determination of these analytes using a normal-phase HILIC column after analyte derivatization. The approach is suitable for neonatal screening follow-ups and monitoring of the treatment for creatine deficiency syndromes.

Keywords: AGAT; Arginine-glycine amidinotransferase; Cerebral creatine deficiency; Creatine; Creatine transporter; GAMT; Guanidinoacetate; Guanidinoacetate methyltransferase; Laboratory diagnosis; Mass spectrometry.

MeSH terms

Creatine*
Glycine / analogs & derivatives
Guanidinoacetate N-Methyltransferase*
Humans
Infant, Newborn
Neonatal Screening
Syndrome
Tandem Mass Spectrometry

Substances

Guanidinoacetate N-Methyltransferase
glycocyamine
Creatine
Glycine