Guanidinoacetate methyltransferase (GAMT) deficiency: non-invasive enzymatic diagnosis of a newly recognized inborn error of metabolism

Ilas, Josenato; Mühl, Adolf; Stöckler‐Ipsiroglu, Sylvia

doi:10.1016/s0009-8981(99)00182-5

Cited by 41 publications

(30 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A Beckman 125 dual pump equipped with a uv detector (166, Beckman) set at 210 nm, an ODS column (250 £ 4.6 mm, 5 m, Beckman), and a Rheodyne 7725i injector with a 50-l loop was used for the elution of creatine [6]. The mobile phase consisted of sodium phosphate dibasic anhydrous (7.1 g), SDS (2 g), distilled water (500 ml), acetonitrile (250 ml), and phosphoric acid to reach a Wnal pH 3; it was Wltered on GH Polypro Wlters before use.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, all of these methods consist of numerous steps (e.g., extraction, puriWcation of the extracts, quantiWcation), require high amounts of cells, and show high unspeciWc blank radioactivity and, therefore, are more useful for detecting GAMT in tissues than in cells with low activity [2]. Ilas et al [6] developed a speciWc and sensitive method to measure GAMT activity in human-cultured Wbroblasts, Epstein-Barr virus-transformed lymphoblasts, and cultivated amniotic cells but still with radiolabeled substrate. In their method, creatine is separated from [ 14 C]guanidinoacetate in HPLC and is quantiWed in a beta counter.…”

mentioning

confidence: 99%

See 1 more Smart Citation

HPLC assay for guanidinoacetate methyltransferase

Alessandrı̀

Celati

Battini

et al. 2004

Analytical Biochemistry

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

HPLC assay for guanidinoacetate methyltransferase

Alessandrı̀

Celati

Battini

et al. 2004

Analytical Biochemistry

View full text Add to dashboard Cite

“…38 The activity of GAMT can be determined in fibroblasts, lymphoblasts, and amniocytes via the formation of creatine from radioactive or stable isotope-labeled guanidinoacetate. 38,62 For CRTR activity, the transport of radioactive isotope-labeled creatine is measured in fibroblasts. Affected patients have <10% normal activity.…”

Section: Measurement Of Agat Gamt and Crtr Activitiesmentioning

confidence: 99%

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

Sharer

Bodamer

Longo

et al. 2017

Genetics in Medicine

View full text Add to dashboard Cite

Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these standards and guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of others that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, clinical laboratory geneticists should apply their professional judgment to the specific circumstances presented by the patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.

show abstract

“…Biochemical findings include high urinary excretion of guanidinoacetate (GAA; immediate precursor of creatine and substrate to deficient enzyme activity), low urinary excretion of creatinine (conversion product of intracellular creatine), and depletion of creatine in brain and muscle (Stöckler et al, 1997;Schulze et al, 2003). Enzymatic diagnosis is possible by the demonstration of deficient GAMT activity in liver, cultivated skin fibroblasts and virustransformed lymphoblasts (Stöckler et al, 1996b;Ilas et al, 2001). Patients with GAMT deficiency have shown favourable response to oral supplementation of creatine monohydrate and dietary restriction of arginine, but in none of them complete reversal of symptoms was observed (Stöckler et al, 1996 a;Stöckler et al 1997;Schulze et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Characterization of seven novel mutations in seven patients with GAMT deficiency

et al. 2004

View full text Add to dashboard Cite

Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive error of creatine synthesis characterized by cerebral creatine deficiency, accumulation of guanidinoacetate, mental retardation, epilepsy and extrapyramidal signs. So far, six mutations have been identified in seven patients. We investigated seven new patients by screening the promoter, 3´UTR, and six exons and exon/intron boundaries using direct sequencing and denaturing gradient gel electrophoresis. The clinical and biochemical phenotype was characterized by scoring the degree of main clinical manifestations and by determination of urinary guanidinoacetate concentrations and of GAMT activity in fibroblasts / lymphoblasts, respectively. We identified 7 novel mutations, including c.64dupG (exon 1; 4/14 alleles); c.59G>C (exon 1; 3/14 alleles); c.491delG (exon 5; 2/14 alleles); c.160G>C (exon 1; 2 / 14 alleles); and c.152A>C (exon 1; 1 / 14 alleles); c.526dupG (exon 5; 1/14 alleles); c.521G>A (exon 5; 1/14 alleles), and two polymorphisms c.626C>T (exon 6) and c.459+71G>A (intron 4). Frameshift and missense mutations in exon 1 were prevalent in the 4 patients with the severe phenotype, however a clear genotype-phenotype correlation has not been established in the limited number of patients characterized so far.

show abstract

Guanidinoacetate methyltransferase (GAMT) deficiency: non-invasive enzymatic diagnosis of a newly recognized inborn error of metabolism

Cited by 41 publications

References 10 publications

HPLC assay for guanidinoacetate methyltransferase

HPLC assay for guanidinoacetate methyltransferase

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

Characterization of seven novel mutations in seven patients with GAMT deficiency

Contact Info

Product

Resources

About