title: Laboratory diagnosis of creatine deficiency syndromes: a technical standard and guideline of the American College of Medical Genetics and Genomics.
abstract: 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.Cerebral creatine deficiency syndromes are neurometabolic conditions characterized by intellectual disability, seizures, speech delay, and behavioral abnormalities. Several laboratory methods are available for preliminary and confirmatory diagnosis of these conditions, including measurement of creatine and related metabolites in biofluids using liquid chromatography-tandem mass spectrometry or gas chromatography-mass spectrometry, enzyme activity assays in cultured cells, and DNA sequence analysis. These guidelines are intended to standardize these procedures to help optimize the diagnosis of creatine deficiency syndromes. While biochemical methods are emphasized, considerations for confirmatory molecular testing are also discussed, along with variables that influence test results and interpretation.Genet Med 19 2, 256-263.
authors.affiliation: Department of Genetics, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Sharer
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Olaf
authors.initials: O
authors.lastname: Bodamer
authors.affiliation: Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Longo
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.|Department of Clinical Genomics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Tortorelli
authors.affiliation: Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mirjam M C
authors.identifier: 0000-0002-9382-613X
authors.initials: MM
authors.lastname: Wamelink
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Young
mesh_terms: D000579:Amidinotransferases / Q000097:blood / Q000134:cerebrospinal fluid / Q000172:deficiency* / Q000235:genetics / Q000652:urine; D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000652:urine; D020739:Brain Diseases, Metabolic, Inborn / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000652:urine; D019411:Clinical Laboratory Techniques / Q000379:methods; D003401:Creatine / Q000097:blood / Q000134:cerebrospinal fluid / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D002658:Developmental Disabilities / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000652:urine; D005820:Genetic Testing / Q000592:standards; D005826:Genetics, Medical / Q000592:standards; D023281:Genomics; D050937:Guanidinoacetate N-Methyltransferase / Q000097:blood / Q000134:cerebrospinal fluid / Q000172:deficiency* / Q000235:genetics / Q000652:urine; D017408:Guidelines as Topic; D006801:Humans; D008607:Intellectual Disability / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000652:urine; D007805:Language Development Disorders / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000652:urine; D038901:X-Linked Intellectual Disability / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000652:urine; D009069:Movement Disorders / Q000097:blood / Q000134:cerebrospinal fluid / Q000151:congenital* / Q000235:genetics / Q000652:urine; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000172:deficiency* / Q000235:genetics / Q000652:urine; D012097:Repressor Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000652:urine; D013064:Speech Disorders / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000652:urine
chemical_list: D050480:Plasma Membrane Neurotransmitter Transport Proteins; D012097:Repressor Proteins; C428128:TFCP2L1 protein, human; C494506:GAMT protein, human; D050937:Guanidinoacetate N-Methyltransferase; D000579:Amidinotransferases; C020681:glycine amidinotransferase; D003401:Creatine