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Quantification of creatine and guanidinoacetate using GC-MS and LC-MS/MS for the detection of cerebral creatine deficiency syndromes.

Authors
Type
Published Article
Journal
Current protocols in human genetics / editorial board, Jonathan L. Haines ... [et al.]
Publication Date
Volume
Chapter 17
Identifiers
DOI: 10.1002/0471142905.hg1703s54
PMID: 18428409
Source
Medline
License
Unknown

Abstract

Inherited defects in creatine biosynthesis and cellular uptake are neurometabolic disorders characterized by seizures, developmental delay, mental retardation, autistic-like behavior, and creatine deficiency in the brain. Metabolic screening of these disorders is possible using analytical techniques that quantify creatine and its precursor guanidinoacetate in urine, plasma, or cerebrospinal fluid (CSF). Elevated creatine in urine is suggestive of a deficiency of the X-linked creatine transporter, SLC6A8. Decreased or elevated levels of guanidinoacetate in urine, plasma, or CSF suggest deficiencies of the creatine biosynthetic enzymes, arginine:glycine amidinotransferase (AGAT) or guanidinoacetate methyltransferase (GAMT), respectively. This unit describes three stable isotope dilution-mass spectrometric methods for analyzing creatine and guanidinoacetate. Gas chromatography/mass spectrometry with negative-ion chemical ionization is a highly sensitive technique, suitable for detection of low analyte levels resulting from AGAT deficiency and in CSF. The two liquid chromatography-tandem mass spectrometric approaches are amenable to high-throughput screening and have simple sample preparation requirements.

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