Membrane phospholipids and high-energy metabolites in childhood ataxia with CNS hypomyelination.
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.
Blüml
S
S
Magnetic Resonance Spectroscopy Unit, Huntington Medical Research Institutes, Pasadena, CA 91105, USA.
Philippart
M
M
Schiffmann
R
R
Seymour
K
K
Ross
B D
BD
D000293:Adolescent; D001259:Ataxia / Q000378:metabolism*; D001834:Body Water; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004734:Energy Metabolism; D005260:Female; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010710:Phosphates / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010766:Phosphorylation
D010710:Phosphates; D010743:Phospholipids