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Korean J Pediatr 2012 October;55(10) :397-402.
Published online 2012 October 15.        doi:
Magnetic resonance imaging and spectroscopic analysis in 5 cases of Pelizaeus-Merzbacher disease:metabolic abnormalities as diagnostic tools
Eun Lee (Lee E)1, Mi-Sun Yum (Yum MS)1, Hae-Won Choi (Choi HW)1, Han-Wook Yoo (Yoo HW)1,2, Su Jeong You (You SJ)3, Eun-Hye Lee (Lee EH)4, Tae-Sung Ko (Ko TS)1
1Department of Pediatrics, Asan Medical Center Childrens Hospital, University of Ulsan College of Medicine, Seoul, Korea
1,2Department of Medical Genetics Clinic and Laboratory, Asan Medical Center Childrens Hospital, University of Ulsan College of Medicine, Seoul,
3Department of Pediatrics, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
4Department of Pediatrics, Kyung Hee University School of Medicine, Seoul, Korea
Corresponding Author: Tae-Sung Ko ,Tel: +82-2-3010-3390, Fax: +82-2-473-3725, Email:
Copyright © 2012 by The Korean Pediatric Society
Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder characterized by dysmyelination in the central nervous system. PMD results from deletion, mutation, or duplication of the proteolipid protein gene (PLP1) located at Xq22, leading to the failure of axon myelination by oligodendrocytes in the central nervous system. PMD may be suspected when there are clinical manifestations such as nystagmus, developmental delays, and spasticity, and genetic analysis can confirm the diagnosis. Further diagnostic manifestations of the disease include a lack of myelination on brain magnetic resonance (MR) imaging and aberrant N-acetyl aspartate (NAA) and choline concentrations that reflect axonal and myelination abnormalities on phroton MR spectroscopy. We report 5 cases of PMD (in 1 girl and 4 boys). PLP1 duplication was detected in 2 patients. Brain MR analyses and MR spectroscopy were performed for all the patients. The brain MR images showed white matter abnormalities typical of PMD, and the MR spectroscopic images showed diverse patterns of NAA, creatinine, and choline concentrations. We propose that MR spectroscopic analysis of metabolic alterations can aid the PMD diagnosis and can contribute to a better understanding of the pathogenesis of the disease.
Keywords: Pelizaeus-Merzbacher disease | Proteolipid protein | Magnetic resonance spectroscopy
1. Woodward KJ. The molecular and cellular defects underlying Pelizaeus-Merzbacher disease. Expert Rev Mol Med 2008;10:e14.
2. Golomb MR, Walsh LE, Carvalho KS, Christensen CK, DeMyer WE. Clinical findings in Pelizaeus-Merzbacher disease. J Child Neurol 2004;19:328–331.
3. Hodes ME, Pratt VM, Dlouhy SR. Genetics of Pelizaeus-Merzbacher disease. Dev Neurosci 1993;15:383–394.
4. Pizzini F, Fatemi AS, Barker PB, Nagae-Poetscher LM, Horska A, Zimmerman AW, et al. Proton MR spectroscopic imaging in Pelizaeus-Merzbacher disease. AJNR Am J Neuroradiol 2003;24:1683–1689.
5. Takanashi J, Sugita K, Osaka H, Ishii M, Niimi H. Proton MR spectroscopy in Pelizaeus-Merzbacher disease. AJNR Am J Neuroradiol 1997;18:533–53
6. Sener RN. Pelizaeus-Merzbacher disease: diffusion MR imaging and proton MR spectroscopy findings. J Neuroradiol 2004;31:138–141.
7. Howe FA, Maxwell RJ, Saunders DE, Brown MM, Griffiths JR. Proton spectroscopy in vivo. Magn Reson Q 1993;9:31–59.
8. Grodd W, Krageloh-Mann I, Klose U, Sauter R. Metabolic and destructive brain disorders in children: findings with localized proton MR spectroscopy. Radiology 1991;181:173–181.
9. Inoue K. PLP1-related inherited dysmyelinating disorders: Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Neurogenetics 2005;6:1–16.
10. Warshawsky I, Chernova OB, Hubner CA, Stindl R, Henneke M, Gal A, et al. Multiplex ligation-dependent probe amplification for rapid detection of proteolipid protein 1 gene duplications and deletions in affected males and carrier females with Pelizaeus-Merzbacher disease. Clin Chem 2006;52:1267–1275.
11. Miller E, Widjaja E, Nilsson D, Yoon G, Banwell B, Blaser S. Magnetic resonance imaging of a unique mutation in a family with Pelizaeus-Merzbacher disease. Am J Med Genet A 2010;152A:748–752.
12. Kolodziejczyk K, Hamilton NB, Wade A, Karadottir R, Attwell D. The effect of N-acetyl-aspartyl-glutamate and N-acetyl-aspartate on white matter oligodendrocytes. Brain 2009;132:1496–1508.
13. Takanashi J, Inoue K, Tomita M, Kurihara A, Morita F, Ikehira H, et al. Brain N-acetylaspartate is elevated in Pelizaeus-Merzbacher disease with PLP1 duplication. Neurology 2002;58:237–241.
14. Kim SJ, Yoon JS, Baek HJ, Suh SI, Bae SY, Cho HJ, et al. Identification of proteolipid protein 1 gene duplication by multiplex ligation-dependent probe amplification: first report of genetically confirmed family of Pelizaeus-Merzbacher disease in Korea. J Korean Med Sci 2008;23:328–331.
15. Lee ES, Moon HK, Park YH, Garbern J, Hobson GM. A case of complicated spastic paraplegia 2 due to a point mutation in the proteolipid protein 1 gene. J Neurol Sci 2004;224:83–87.
16. Kim SM, Lee BC, Kwon KH, Kim SY, Yoo KH, Jung S, et al. Pelizaeus-Merzbacher disease: two cases in a family diagnosed by the clinical features and magnetic resonance imaging. J Korean Neurol Assoc 1995;13:115–122.
17. Kang HS, Oh SW, Park YW, Lee CG, Kim SW, Lee GJ. Two cases of Pelizaeus-Merzbacher disease. J Korean Pediatr Soc 2000;43:561–566.
18. Seitelberger F. Neuropathology and genetics of Pelizaeus-Merzbacher disease. Brain Pathol 1995;5:267–273.
19. Urenjak J, Williams SR, Gadian DG, Noble M. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 1993;13:981–989.
20. Spalice A, Popolizio T, Parisi P, Scarabino T, Iannetti P. Proton MR spectroscopy in connatal Pelizaeus-Merzbacher disease. Pediatr Radiol 2000;30:171–175.
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