Abstract
Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive genetic disorder which results in global developmental delay and intellectual disability. There is evidence that early treatment prevents intellectual disability and seizures. GAMT deficiency is now being discussed as a potential addition to the U.S. Recommended Uniform Screening Panel (RUSP); the availability of suitable screening methods must be considered. A neonatal screening derivatized method to quantify creatine (CRE) and guanidinoacetic acid (GAA) in dried blood spots by tandem mass spectrometry (MS/MS) has been described. Its key feature is the ability to detect CRE and GAA in the same extract generated from neonatal DBS during amino acids (AA) and acylcarnitines (AC) analysis. More laboratories are adopting non-derivatized MS/MS screening methods. We describe an improved, non-derivatized DBS extraction and MS/MS analytical method (AAAC-GAMT) which incorporates quantitation of CRE and GAA into routine analysis of amino acids, acylcarnitines, and succinylacetone. The non-derivatized AAAC-GAMT method performs comparably to the stand-alone GAMT and non-derivatized AAAC screening methods, evidencing its potential suitability for high-throughput GAMT neonatal screening.
Highlights
Guanidinoacetate methyltransferase (GAMT) deficiency (OMIM 612736) is an autosomal recessive genetic disorder which results in global developmental delay and intellectual disability [1,2]
We used the method to quantitate these biomarkers in quality control (QC) DBS specimens produced at the Centers for Disease Control and Prevention’s (CDC) Newborn Screening Quality Assurance Program and characterized for amino acids (AA), AC, SUAC, CRE, and guanidinoacetic acid (GAA) via previously described methods [7]
Three additional QC pools enriched with CRE and GAA were used as low (A1512), medium (C1512), and high (E1512) QC for means comparison
Summary
Guanidinoacetate methyltransferase (GAMT) deficiency (OMIM 612736) is an autosomal recessive genetic disorder which results in global developmental delay and intellectual disability [1,2]. It is due to a disorder of creatine synthesis caused by deficiency of guanidine acetate methyltransferase, resulting in a lack of creatine (CRE) and an accumulation of guanidinoacetic acid (GAA), the biochemical precursor of creatine [3,4]. One key feature is the ability to detect CRE and GAA in the same extract from neonatal DBS’s using the classical (i.e., derivatized) method using flow injection–tandem mass spectrometry. Non-derivatized DBS extraction and flow injection–tandem mass spectrometry analytical method that incorporates quantitation of CRE and GAA into a routine analysis of amino acids (AA), acylcarnitines (AC), and succinylacetone (SUAC). We describe the method’s precision, linearity, and limit of detection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
