LC-MS/MS measurements of urinary guanidinoacetic acid and creatine: Method optimization by deleting derivatization step

Rucheton, Benoît; Mesli, Samir; Boutin, Julian; Amintas, Samuel; Colombies, B.; Ducint, Dominique; Redonnet‐Vernhet, Isabelle

doi:10.1016/j.cca.2019.03.007

Cited by 5 publications

(3 citation statements)

References 18 publications

(28 reference statements)

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“…MRS also provides a non-invasive tool to evaluate the degree of cerebral Cr recovery in the follow-up of children. LC-MS/MS could be used to screen blood/urine for metabolite deficiencies to identify patients with suspected CCDS ( 8 , 9 ). Genetic testing should be used to make a definitive diagnosis and MRS can confirm that a variant is pathogenic as a functional test.…”

Section: Discussionmentioning

confidence: 99%

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Fourteen cases of cerebral creatine deficiency syndrome in children: a cohort study in China

Sun¹,

Wang²,

Wu³

et al. 2023

Transl Pediatr

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Background This study sought to analyze the clinical characteristics, biochemical metabolic indications, treatment results, and genetic spectrum of cerebral creatine deficiency syndrome (CCDS), estimate the prevalence of CCDS in Chinese children and provide a reference to guide clinical practice. Methods We performed a retrospective cohort study of 3,568 children with developmental delay at Children’s Hospital of Fudan University over a 6-year period (January 2017–December 2022). Metabolites in the blood/urine were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and genetic testing was performed by next-generation sequencing (NGS). The patients with suspected CCDS were ultimately diagnosed by magnetic resonance spectroscopy (MRS). The patients were then treated and followed up. All the reported cases of CCDS, their gene mutations, and treatment results in China were summarized. Results Ultimately, 14 patients were diagnosed with CCDS. The age of onset was between 1–2 years. All the patients had developmental delay, 9 had epilepsy, and 8 had movement or behavioral disorders. A total of 17 genetic variants were identified, including 6 novel variants. c.403G>A, c.491dupG of the guanidinoacetate methyltransferase ( GAMT ) gene had a relatively high frequency. After treatment, patients with GAMT deficiency showed obvious improvements, and brain creatine (Cr) levels recovered to 50–80% of normal, 1 patient achieved normal neurodevelopment, and 3 patients became epilepsy free; however, 6 male patients with X-linked creatine transporter gene ( SLC6A8 ) variants received Cr for 3–6 months with no effect, and 2 patients received combined therapy with few improvements. Conclusions The prevalence of CCDS is ~0.39% in Chinese children with developmental delay. A low-protein diet, Cr and, ornithine were useful for patients with GAMT deficiency. Male patients with SLC6A8 deficiency showed only limited improvement on combined therapy.

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Section: Discussionmentioning

confidence: 99%

“…Cr and GAA levels on DBS and the Cr/Crn ratio in the urine both were measured by LC-MS/MS (Acquity UHPLC-class Xevo TQD, Waters, USA) ( 8 , 9 ). The peripheral blood of the patients with suspected CCDS and their parents were obtained for next-generation sequencing (NGS).…”

Section: Methodsmentioning

confidence: 99%

Fourteen cases of cerebral creatine deficiency syndrome in children: a cohort study in China

Sun¹,

Wang²,

Wu³

et al. 2023

Transl Pediatr

View full text Add to dashboard Cite

show abstract

“…Biochemical assays for GAA and creatine levels were performed in the Laboratory for Genetic Metabolic Diseases at Amsterdam University Medical Centres (Amsterdam, Netherlands). A similar UPLC MS/MS method as described by Benoit et al [ 14 ] was used to measure guanidinoacetate and creatine using an ion-pair (heptafluorobutyric acid) UPLC-system with a BEH-C18 column to separate the underivatized metabolites and measure them by monitoring specific transitions employing stable isotope labeled internal standards.…”

Section: Methodsmentioning

confidence: 99%

Adult GAMT deficiency: A literature review and report of two siblings

Modi

Khan

Lee

et al. 2021

Molecular Genetics and Metabolism Reports

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Guanidinoacetate methyltransferase (GAMT) deficiency is a creatine deficiency disorder and an inborn error of metabolism presenting with progressive intellectual and neurological deterioration. As most cases are identified and treated in early childhood, adult phenotypes that can help in understanding the natural history of the disorder are rare. We describe two adult cases of GAMT deficiency from a consanguineous family in Pakistan that presented with a history of global developmental delay, cognitive impairments, excessive drooling, behavioral abnormalities, contractures and apparent bone deformities initially presumed to be the reason for abnormal gait. Exome sequencing identified a homozygous nonsense variant in GAMT : NM_000156.5:c.134G>A (p.Trp45*). We also performed a literature review and compiled the genetic and clinical characteristics of all adult cases of GAMT deficiency reported to date. When compared to the adult cases previously reported, the musculoskeletal phenotype and the rapidly progressive nature of neurological and motor decline seen in our patients is striking. This study presents an opportunity to gain insights into the adult presentation of GAMT deficiency and highlights the need for in-depth evaluation and reporting of clinical features to expand our understanding of the phenotypic spectrum.

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

Liu

Sun

2022

Clinical Applications of Mass Spectrometry in Biomolecular Analysis

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LC-MS/MS measurements of urinary guanidinoacetic acid and creatine: Method optimization by deleting derivatization step

Cited by 5 publications

References 18 publications

Fourteen cases of cerebral creatine deficiency syndrome in children: a cohort study in China

Fourteen cases of cerebral creatine deficiency syndrome in children: a cohort study in China

Adult GAMT deficiency: A literature review and report of two siblings

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

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