Author:
Blüml S.,Philippart M.,Schiffmann R.,Seymour K.,Ross B. D.
Abstract
Background: Childhood ataxia with CNS hypomyelination (CACH) is a leukodystrophy with extreme rarefaction of white matter caused by mutations in one of the five subunits of the translation initiation factor 2B (eIF2B).Methods: Seven children with this disease and nine age-matched control subjects were studied with proton-decoupled phosphorus magnetic resonance (MR) spectroscopy.Results: In patients with CACH, cerebral concentrations of high-energy phosphate metabolites were abnormal. Of the metabolites involved in biosynthesis and catabolism of membrane phospholipids, glycerophosphorylethanolamine was reduced (0.24 ± 0.18 mmol/kg brain vs 0.44 ± 0.14; p < 0.02), and phosphorylethanolamine was increased (2.32 ± 0.53 vs 1.53 ± 0.22; p < 0.01), whereas the choline-containing phosphorylated metabolites were unchanged. Nucleoside triphosphate (NTP) was reduced (2.44 ± 0.34 mmol/kg brain tissue vs 3.09 ± 0.58; p < 0.01), phosphocreatine was elevated (4.11 ± 0.63 vs 3.27 ± 0.33; p < 0.01), and inorganic phosphate was reduced (0.77 ± 0.32 vs 1.06 ± 0.26; p < 0.05). Intracellular pH was elevated in patients (7.03 ± 0.04 vs 6.99 ± 0.02; p < 0.02).Conclusions: The authors found an altered energy state of the residual cell population investigated. Together with previously identified replacement of white matter by CSF, the present findings raise the possibility that the genetic defect in eIF2B may result in impairment of myelin membrane synthesis or myelin membrane transport in the in vivo CACH brain. Ethanolamine metabolites constitute the plasmalogens, and the present findings may include a defect in plasmalogen metabolism.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
27 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. MR Spectroscopy in Health and Disease;Handbook of the Cerebellum and Cerebellar Disorders;2021-12-05
2. Proton and Multinuclear Spectroscopy of the Pediatric Brain;Magnetic Resonance Imaging Clinics of North America;2021-11
3. MRI Natural History of the Leukodystrophy Vanishing White Matter;Radiology;2021-09
4. MR Spectroscopy in Health and Disease;Handbook of the Cerebellum and Cerebellar Disorders;2021
5. Astroglia in Leukodystrophies;Neuroglia in Neurodegenerative Diseases;2019