Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes

Continuous Age- and Sex-Adjusted Reference Intervals of Urinary Markers for Cerebral Creatine Deficiency Syndromes: A Novel Approach to the Definition of Reference Intervals

“…True positive samples were diagnosed with either AGAT (n ϭ 3), GAMT (n ϭ 32), or CRT deficiency (n ϭ 120). At least 84 of these cases have been reported previously in peer- reviewed publications (13)(14), and all were confirmed by combinations of molecular analysis, magnetic resonance spectroscopy, and enzymatic analysis. The specimens included in this study were collected before treatment.…”

Prevalence of Creatine Deficiency Syndromes in Children With Nonsyndromic Autism

“…9 To date, there are 6, 50, and 88 pathogenic mutations described throughout GATM, GAMT, and SLC6A8 genes, respectively. 18,19 A clinical diagnosis of CDS is based on the determination of an abnormal ratio of creatine-to-creatinine and guanidinoacetate-to-creatinine in spot urine; altered excretion of creatine, guanidinoacetate, and creatinine measured in 24-houre urine collections; altered concentration of these metabolites in blood, or depletion of creatine in brain assessed with in vivo magnetic resonance (MR) spectroscopy. 9,20,21 Each of the disorders has a pathognomonic biochemical phenotype that allows the differentiation between them.…”

Laboratory diagnosis of creatine deficiency syndromes: a technical standard and guideline of the American College of Medical Genetics and Genomics

“…In the event of an abnormal metabolite test result, repeat analysis is recommended because of the relatively low specificity of elevated urinary creatine in the diagnosis of creatine transporter deficiency, and low guanidinoacetate and creatine concentrations in AGAT deficiency. 36,37 Definitive confirmation of the diagnosis requires DNA sequencing of the appropriate gene and (if molecular analysis is ambiguous) measurement of AGAT or GAMT enzyme activity or of CRTR-mediated transport. Confirmation by these methods is important because other conditions (see below) may cause altered concentrations of creatine and guanidinoacetate in plasma and urine.…”