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.

Early Indicators of Creatine Transporter Deficiency

“…Urine screens are not perfect, but can be effective as early as age 1 month; see recent ACMG guidelines. 2 However, most of our participants were diagnosed after a seizure or only after years of delayed development. While this study is limited to retrospective parent report and medical record review, it is informative since the sample comprises possibly ~10% of all known cases, and it presents the first in-depth look at the sequence of events that ultimately led to an accurate diagnosis.…”

“…Preliminary diagnosis is possible by measuring creatine and related metabolites in blood and/or urine, or by proton magnetic resonance spectroscopy. 2 Definitive diagnosis is made by sequencing SLC6A8 and creatine uptake studies. CTD does not result in imminently life-threatening conditions early in life.…”

A novel mutation in two cousins with guanidinoacetate methyltransferase (GAMT) deficiency presented with autism

“…High GAA levels in urine and plasma are characteristic of GAMT deficiency, whereas abnormally low GAA levels in urine and plasma are typical of AGAT deficiency, Normal GAA levels in urine and plasma and increased urine creatine/creatinine ratio is consistent with CRTR deficiency. 10 The high GAA levels in urine and normal urine creatine/ creatinine ratio detected in our index patient were characteristic for GAMT deficiency.…”

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

“…Thus, examining structural determinants of substrate binding in the CRT will provide a deeper understanding of the regulation of Cr uptake as well as novel therapeutic ligands [248,278]. For a more detailed coverage, both on human pathology and on their different in vivo models (KO and KI mice and rats), of the genetic conditions (AGAT, GAMT, and SLC6A8 deficiencies) of the Cr deficiency syndrome please refer to [18,22,279].…”