1H MR spectroscopy as a diagnostic tool for cerebral creatine deficiency
- 26 August 2008
- journal article
- case report
- Published by Springer Science and Business Media LLC in Magnetic Resonance Materials in Physics, Biology and Medicine
- Vol. 21 (5), 327-332
- https://doi.org/10.1007/s10334-008-0137-z
Abstract
Total creatine (tCr) constitutes one of the most prominent signals in human brain MR spectra. A significant decrease in the tCr signal indicates a severe disorder of creatine metabolism. We describe the potential of 1H MR spectroscopy in differential diagnosis of creatine transporter (SLC6A8) deficiency syndrome. Two siblings, a 7-year-old female presenting with mild psychomotor delay, and a 5-year-old male with severe psychomotor retardation, epilepsy and autistic spectrum of problems including speech delay, underwent MR examination because of suspected creatine deficiency. After the MRI examination, 1H MR spectroscopy using the CSI technique was performed. Metabolic images of N-acetylaspartate, tCr and choline concentrations showed a very low tCr signal in the male, which was approximately three times lower than in his sister (male/female/controls: tCr = 1.6/4.6/7.5 mM). Despite creatine supplementation, no improvement in clinical status and tCr concentration in the MR spectra of the male was observed and diagnosis of SLC6A8 deficiency was proposed. Sequence analysis of the SLC6A8 gene revealed a novel pathogenic frameshift mutation c.219delC; p.Asn74ThrfsX23, hemizygous in the male and heterozygous in the female. The diagnosis of X-linked mental retardation caused by the SLC6A8 deficiency can be independently established by 1H MR spectroscopy.This publication has 25 references indexed in Scilit:
- X‐linked creatine transporter defect: A report on two unrelated boys with a severe clinical phenotypeJournal of Inherited Metabolic Disease, 2006
- Error images for spectroscopic imaging by LCModel using Cramer–Rao boundsMagnetic Resonance Materials in Physics, Biology and Medicine, 2006
- ProtonT2 relaxation of cerebral metabolites of normal human brain over largeTE rangeNMR in Biomedicine, 2005
- Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscleMolecular Genetics and Metabolism, 2004
- Lack of creatine in muscle and brain in an adult with GAMT deficiencyAnnals of Neurology, 2003
- Congenital Creatine Transporter DeficiencyNeuropediatrics, 2002
- X‐linked creatine deficiency syndrome: A novel mutation in creatine transporter gene SLC6A8Annals of Neurology, 2002
- X-Linked Creatine-Transporter Gene (SLC6A8) Defect: A New Creatine-Deficiency SyndromeAmerican Journal of Human Genetics, 2001
- Irreversible brain creatine deficiency with elevated serum and urine creatine: A creatine transporter defect?Annals of Neurology, 2001
- Estimation of metabolite concentrations from localized in vivo proton NMR spectraMagnetic Resonance in Medicine, 1993