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

Genet Med. 2017 Feb;19(2):256-263. doi: 10.1038/gim.2016.203. Epub 2017 Jan 5.

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.

MeSH terms

  • Amidinotransferases / blood
  • Amidinotransferases / cerebrospinal fluid
  • Amidinotransferases / deficiency*
  • Amidinotransferases / genetics
  • Amidinotransferases / urine
  • Amino Acid Metabolism, Inborn Errors / blood
  • Amino Acid Metabolism, Inborn Errors / cerebrospinal fluid
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Amino Acid Metabolism, Inborn Errors / urine
  • Brain Diseases, Metabolic, Inborn / blood
  • Brain Diseases, Metabolic, Inborn / cerebrospinal fluid
  • Brain Diseases, Metabolic, Inborn / genetics*
  • Brain Diseases, Metabolic, Inborn / urine
  • Clinical Laboratory Techniques / methods
  • Creatine / blood
  • Creatine / cerebrospinal fluid
  • Creatine / deficiency*
  • Creatine / genetics
  • Creatine / metabolism*
  • Creatine / urine
  • Developmental Disabilities / blood
  • Developmental Disabilities / cerebrospinal fluid
  • Developmental Disabilities / genetics
  • Developmental Disabilities / urine
  • Genetic Testing / standards
  • Genetics, Medical / standards
  • Genomics
  • Guanidinoacetate N-Methyltransferase / blood
  • Guanidinoacetate N-Methyltransferase / cerebrospinal fluid
  • Guanidinoacetate N-Methyltransferase / deficiency*
  • Guanidinoacetate N-Methyltransferase / genetics
  • Guanidinoacetate N-Methyltransferase / urine
  • Guidelines as Topic
  • Humans
  • Intellectual Disability / blood
  • Intellectual Disability / cerebrospinal fluid
  • Intellectual Disability / genetics*
  • Intellectual Disability / urine
  • Language Development Disorders / blood
  • Language Development Disorders / cerebrospinal fluid
  • Language Development Disorders / genetics*
  • Language Development Disorders / urine
  • Mental Retardation, X-Linked / blood
  • Mental Retardation, X-Linked / cerebrospinal fluid
  • Mental Retardation, X-Linked / genetics*
  • Mental Retardation, X-Linked / urine
  • Movement Disorders / blood
  • Movement Disorders / cerebrospinal fluid
  • Movement Disorders / congenital*
  • Movement Disorders / genetics
  • Movement Disorders / urine
  • Plasma Membrane Neurotransmitter Transport Proteins / blood
  • Plasma Membrane Neurotransmitter Transport Proteins / cerebrospinal fluid
  • Plasma Membrane Neurotransmitter Transport Proteins / deficiency*
  • Plasma Membrane Neurotransmitter Transport Proteins / genetics
  • Plasma Membrane Neurotransmitter Transport Proteins / urine
  • Repressor Proteins / blood
  • Repressor Proteins / cerebrospinal fluid
  • Repressor Proteins / genetics*
  • Repressor Proteins / urine
  • Speech Disorders / blood
  • Speech Disorders / cerebrospinal fluid
  • Speech Disorders / genetics*
  • Speech Disorders / urine

Substances

  • Plasma Membrane Neurotransmitter Transport Proteins
  • Repressor Proteins
  • TFCP2L1 protein, human
  • GAMT protein, human
  • Guanidinoacetate N-Methyltransferase
  • Amidinotransferases
  • glycine amidinotransferase
  • Creatine

Supplementary concepts

  • Arginine-Glycine Amidinotransferase Deficiency
  • Creatine deficiency, X-linked
  • Guanidinoacetate methyltransferase deficiency