Skip to main content
SpringerLink
Log in

Childhood Mitochondrial Disorders and Other Inborn Errors of Metabolism Presenting With White Matter Disease

  • Chapter
Bioimaging in Neurodegeneration

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Advances in neuroimaging, particularly magnetic resonance imaging (MRI), have made possible the study of normal and abnormal brain myelination. Although many disorders present with nonspecific MRI findings, more detailed analysis with newer imaging modalities such as diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and magnetization transfer imaging (MTI), allow detailed investigation of white matter microstructure, abnormalities that may precede and evade detection on conventional MRI. The purpose of this chapter is to discuss the utility of neuroimaging in the study and differentiation of mitochondrial disorders and other inborn errors of metabolism. The first section will discuss imaging modalities used and their application in the diagnosis and study of metabolic disease. The second section will focus on some characteristic disorders in which abnormal white matter is visualized on neuroimaging. Although not meant to be an exhaustive summary, several key disorders and their clinical and neuroimaging features will be presented. Finally, a table as well as some examples will serve to solidify the differentiation between the disorders and illustrate the best neuroimaging modalities with which to investigate etiology and, in some cases, follow disease progression and response to therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hashemi RJ, Bradley WG Jr. MRI the Basics. Baltimore: Lippincott, Williams and Wilkins; 1997.

    Google Scholar 

  2. Basser PJ. Inferring micro structural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 1995;8:333–344.

    Article  PubMed  CAS  Google Scholar 

  3. Wieshmann UC, Clark CA, Symms MR, et al. Reduced anisotropy of water diffusion in structural cerebral abnormalities demonstrated with diffusion tensor imaging. Magn Reson Imaging 1999;17:1269–1274.

    Article  PubMed  CAS  Google Scholar 

  4. Moser HW, Loes DJ, Melhem ER, et al: X-Linked adrenoleukodystrophy: overview and prognosis as a function of age and brain magnetic resonance imaging abnormality. A study involving 372 patients. Neuropediatrics 2000; 31: 227–239.

    Article  PubMed  CAS  Google Scholar 

  5. Eichler FS, Itoh R, Barker PB, et al. Proton MR spectroscopic and diffusion tensor brain mr imaging in X-linked adrenoleukodystrophy: initial experience. Radiology 2002;225:245–252.

    Article  PubMed  Google Scholar 

  6. Pfeuffer J, Tkac I, Provencher SW, Gruetter R. Toward an in vivo neurochemical profile: quantification of 18 metabolites in short-echo-time (1)H NMR spectra of the rat brain. J Magn Reson 1999;14:104–120.

    Article  Google Scholar 

  7. Tkac I, Andersen P, Adriany G, et al. In vivo 1H NMR Spectroscopy of the human brain at 7T. Magn Reson Med 2001;46:451–456.

    Article  PubMed  CAS  Google Scholar 

  8. deGrauw TJ, Cecil KM, Byars AW, Salomons GS. The clinical syndrome of creatine transporter deficiency. Mol Cell Biochem 2003; 244:45–48.

    Article  PubMed  CAS  Google Scholar 

  9. Weglage J, Wiedermann D, Denecke J, et al. Individual blood-brain barrier phenylalanine transport determines clinical outcome in phenylketonuria. J Inherit Metab Dis 2002;25:431–436.

    Article  PubMed  CAS  Google Scholar 

  10. Jan W, Zimmerman RA, Wang ZJ, et al. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology 2003;45:393–399.

    Article  PubMed  Google Scholar 

  11. Choi CG, Yoo HW. Localized proton MR spectroscopy in infants with urea cycle defect. AJNR 2001;22: 834–837.

    PubMed  CAS  Google Scholar 

  12. Takanashi J, Kurihara A, Tomita M, et al. Distinctly abnormal brain metabolism in late onset ornithine transcarbamylase deficiency. Neurology 2002;59:210–214.

    PubMed  CAS  Google Scholar 

  13. Cross JH, Gadian DG, Connelly A, Leonard JV. Proton magnetic resonance spectroscopy studies in lactic acidosis and mitochondrial disorders. J Inherit Metab Dis 1993;16:800–811.

    Article  PubMed  CAS  Google Scholar 

  14. Sylvain M, Mitchel GA, Shevell MI, et al. Muscle and brain magnetic resonance spectroscopy (MRS) and imaging (MRI) in children with Leigh’s syndrome associated with cytochrome C oxidase deficiency: dependence on findings on clinical status. Ann Neurol 1993; 54:464.

    Google Scholar 

  15. Harada M, Tanouchi M, Arai K, et al. Therapeutic efficacy of a case of pyruvate dehydrogenase complex deficiency monitored by localized proton magnetic resonance spectroscopy. Magn Reson Imaging 1996;14:129–133.

    Article  PubMed  CAS  Google Scholar 

  16. Shevell MI, Didomenicantonio G, Sylvain M, et al. Glutaric academia type II: neuroimaging and spectroscopy evidence for developmental encephalomyopathy. Pediatr Neurol 1995;12:350–353.

    Article  PubMed  CAS  Google Scholar 

  17. Lin DD, Crawford TO, Barker PB. Proton MR spectroscopy in the diagnostic evaluation of suspected mitochondrial disease. AJNR Am J Neuroradiol 2003;24:33–41.

    PubMed  Google Scholar 

  18. Choi CG, Yoo HW. Localized proton MR spectroscopy in infants with urea cycle defect. AJNR Am J Neuroradiol 2001;22:834–837.

    PubMed  CAS  Google Scholar 

  19. Takanashi J, Kurihara A, Tomita M, et al: Distinctly abnormal brain metabolism in late onset ornithine transcarbamylase deficiency. Neurology 2002;59:210–214.

    PubMed  CAS  Google Scholar 

  20. Gabis L, Parton P, Roche P, et al. In vivo 1H magnetic resonance spectroscopic measurement of brain glycine levels in nonketotic hyperglycinemia. J Neuroimaging 2001;11:209–211.

    PubMed  CAS  Google Scholar 

  21. Viola A, Chabrol B, Nicoli F, et al. Magnetic resonance spectroscopy study of glycine pathways in nonketotic hyperglycinemia. Pediatr Res 2002;52:292–300.

    PubMed  CAS  Google Scholar 

  22. Jakobs C, Jaeken J, Gibson KM, et al. Inherited disorders of GABA metabolism. 1993; J Inherit Metab Dis 16:704–715.

    Google Scholar 

  23. Bluml S, Philippart M, Schiffman R, et al: Membrane phospholipids and high energy metabolites in childhood ataxia and CNS hypomyelination. Neurology 2003;61:648–654.

    PubMed  CAS  Google Scholar 

  24. Gillies RJ, Barry JA, Ross BD: In vitro and in vivo 13C and 31P NMR analyses of phosphocholine metabolism in rat glioma cells. Magn Reson Med. 1994;32:310–318.

    Article  PubMed  CAS  Google Scholar 

  25. Shapiro EG, Lockman LA, Knopman D, Krivit W. Characteristics of the dementia in late-onset metachromatic leukodystrophy. Neurology 1994;44:662–665.

    PubMed  CAS  Google Scholar 

  26. Cengiz N, Ozbenli T, Onar M, Yildiz L, Ertas B. Adult metachromatic leukodystrophy: three cases with normal nerve conduction velocities in a family. Acta Neurol Scand 2002;105:454–457.

    Article  PubMed  CAS  Google Scholar 

  27. Kihara H. Genetic heterogeneity in metachromatic leukodystrophy. Am J Hum Genet 1982;34:171–181.

    PubMed  CAS  Google Scholar 

  28. Waltz G, Harik SI, Kaufman B. Adult metachromatic leukodystrophy: value of computed tomographic scanning and magnetic resonance imaging of the brain. Arch Neurol 1987;44:225–227.

    PubMed  CAS  Google Scholar 

  29. Felice KJ, Gomez-Lira M, Natowicz M, Grunnet ML, Tsongalis GJ, Sima AA, Kaplan RF. Adult-onset MLD: a gene mutation with isolated polyneuropathy. Neurology 2000;55:1036–1039.

    PubMed  CAS  Google Scholar 

  30. Coulter-Mackie MB, Applegarth DA, Toone JR, Gagnier L, Anzarut AR, Hendson G. Isolated peripheral neuropathy in atypical metachromatic leukodystrophy: a recurrent mutation. Can J Neurol Sci 2002; 29:159–163.

    PubMed  Google Scholar 

  31. Bostantjopoulou S, Katsarou Z, Michelakaki H, Kazis A. Seizures as a presenting feature of late onset metachromatic leukodystrophy. Acta Neurol Scand 2000;102:192–195.

    Article  PubMed  CAS  Google Scholar 

  32. Austin J, Armstrong D, Fouch S, Mitchell C, Stumpf DA, Shearer L, Briner O. Metachromatic leukodystrophy (MLD). VIII. MLD in adults: diagnosis and pathogenesis. Arch Neurol 1968;18:225–240.

    PubMed  CAS  Google Scholar 

  33. Kim TS, Kim IO, Kim WS, Choi YS, Lee JY, Kim OW, Yeon KM, Kim KJ, Hwang YS. MR of childhood metachromatic leukodystrophy. AJNR Am J Neuroradiol 1997;18:733–738.

    PubMed  CAS  Google Scholar 

  34. Zafeiriou DI, Kontopoulos EE, Michelakakis HM, Anastasiou AL, Gombakis NP. Neurophysiology and MRI in late-infantile metachromatic leukodystrophy. Pediatr Neurol 1999;21:843–846.

    Article  PubMed  CAS  Google Scholar 

  35. Faerber EN, Melvin J, Smergel EM MRI appearances of metachromatic leukodystrophy. Pediatr Radiol 1999; 29:669–672.

    Article  PubMed  CAS  Google Scholar 

  36. Salmon E, Van der Linden M, Maerfens Noordhout A, Brucher JM, Mouchette R, Waltregny A, Degueldre C, Franck G. Early thalamic and cortical hypometabolism in adult-onset dementia due to metachromatic leukodystrophy. Acta Neurol Belg. 1999;99:185–188.

    PubMed  CAS  Google Scholar 

  37. Sener RN. Metachromatic leukodystrophy. Diffusion MR imaging and proton MR spectroscopy. Acta Radiol 2003; 44:440–443.

    Article  PubMed  CAS  Google Scholar 

  38. Kruse B, Hanefeld F, Christen HJ, Bruhn H, Michaelis T, Hanicke W, Frahm J. Alterations of brain metabolites in metachromatic leukodystrophy as detected by localized proton magnetic resonance spectroscopy in vivo. J Neurol 1993;241:68–74.

    Article  PubMed  CAS  Google Scholar 

  39. Sener RN. Metachromatic leukodystrophy: diffusion MR imaging findings. AJNR Am J Neuroradiol 2002; 23:1424–1426.

    PubMed  Google Scholar 

  40. Solders G, Celsing G, Hagenfeldt L, Ljungman P, Isberg B, Ringden O. Improved peripheral nerve conduction, EEG and verbal IQ after bone marrow transplantation for adult metachromatic leukodystrophy. Bone Marrow Transplant 1998;22:1119–1122.

    Article  PubMed  CAS  Google Scholar 

  41. Landrieu P, Blanche S, Vanier MT, Metral S, Husson B, Sandhoff K, Fischer A.Bone marrow transplantation in metachromatic leukodystrophy caused by saposin-B deficiency: a case report with a 3-year follow-up period. J Pediatr 1998;133:129–32.

    Article  PubMed  CAS  Google Scholar 

  42. Malm G, Ringden O, Winiarski J, Grondahl E, Uyebrant P, Eriksson U, Hakansson H, Skjeldal O, Mansson JE. Clinical outcome in four children with metachromatic leukodystrophy treated by bone marrow transplantation. Bone Marrow Transplant 1996;17:1003–1008.

    PubMed  CAS  Google Scholar 

  43. Stillman AE, Krivit W, Shapiro E, Lockman L, Latchaw RE. Serial MR after bone marrow transplantation in two patients with metachromatic leukodystrophy. AJNR Am J Neuroradiol 1994;15:1929–1932.

    PubMed  CAS  Google Scholar 

  44. Korn-Lubetzki I, Dor-Wollman T, Soffer D, Raas-Rothschild A, Hurvitz H, Nevo Y. Early peripheral nervous system manifestations of infantile Krabbe disease. Pediatr Neurol 2003;28:115–118.

    Article  PubMed  Google Scholar 

  45. Sabatelli M, Quaranta L, Madia F, Lippi G, Conte A, Lo Monaco M, Di Trapani G, Rafi MA, Wenger DA, Vaccaro AM, Tonali P. Peripheral neuropathy with hypomyelinating features in adult-onset Krabbe’s disease. Neuromusc Disord 2002;12:386–391.

    Article  PubMed  CAS  Google Scholar 

  46. Zlotogora J, Chakraborty S, Knowlton RG, Wenger DA. Krabbe disease locus mapped to chromosome 14 by genetic linkage. Am J Hum Genet 1990;47:37–44.

    PubMed  CAS  Google Scholar 

  47. Cannizzaro LA, Chen YQ, Rafi MA, Wenger DA. Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization. Cytogenet. Cell Genet 1994;66:244–245.

    PubMed  CAS  Google Scholar 

  48. Matsuda J, Vanier MT, Saito Y, Tohyama J, Suzuki K, Suzuki K. A mutation in the saposin A domain of the sphingolipid activator protein (prosaposin) gene results in a late-onset, chronic form of globoid cell leukodystrophy in the mouse. Hum Mol Genet 2001;10:1191–1199.

    Article  PubMed  CAS  Google Scholar 

  49. Furuya H, Kukita Y, Nagano S, Sakai Y, Yamashita Y, Fukuyama H, et al. Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients. Hum Genet 1997;100:450–456.

    Article  PubMed  CAS  Google Scholar 

  50. De Gasperi R, Sosa MAG, Sartorato EL, Battistini S, MacFarlane H, Gusella, JF, Krivit W, Kolodny EH. Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy. Am J Hum Genet 1996;59: 1233–1242.

    PubMed  Google Scholar 

  51. Wenger DA, Rafi MA, Luzi P. Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications. Hum Mutat 1997;10:268–279.

    Article  PubMed  CAS  Google Scholar 

  52. Zlotogora, J Regev, R.; Zeigler, M.; Iancu, T. C.; Bach, G. Krabbe disease: increased incidence in a highly inbred community. Am J Med Genet 1985;21:765–770.

    Article  PubMed  CAS  Google Scholar 

  53. Finelli DA, Tarr RW, Sawyer RN, Horwitz SJ. Deceptively normal MR in early infantile Krabbe disease. AJNR Am J Neuroradiol 1994;;15:167–171.

    PubMed  Google Scholar 

  54. Choi S, Enzmann DR.Infantile Krabbe disease: complementary CT and MR findings. AJNR Am J Neuroradiol 1993;14:1164–1166.

    PubMed  CAS  Google Scholar 

  55. Kwan E, Drace J, Enzmann D. Specific CT findings in Krabbe disease. AJR Am J Roentgenol 1984;143: 665–670.

    PubMed  CAS  Google Scholar 

  56. Zafeiriou DI, Anastasiou AL, Michelakaki EM, Augoustidou-Savvopoulou PA, Katzos GS, Kontopoulos EE. Early infantile Krabbe disease: deceptively normal magnetic resonance imaging and serial neurophysiological studies. Brain Dev 1997;19:488–491.

    Article  PubMed  CAS  Google Scholar 

  57. Sasaki M, Sakuragawa N, Takashima S, Hanaoka S, Arima M. MRI and CT findings in Krabbe disease. Pediatr Neurol 1991;7:283–288.

    Article  PubMed  CAS  Google Scholar 

  58. Farley TJ, Ketonen LM, Bodensteiner JB, Wang DD. Serial MRI and CT findings in infantile Krabbe disease. Pediatr Neurol 1992;8:455–458.

    Article  PubMed  CAS  Google Scholar 

  59. Barone R, Bruhl K, Stoeter P, Fiumara A, Pavone L, Beck M. Clinical and neuroradiological findings in classic infantile and late-onset globoid-cell leukodystrophy (Krabbe disease). Am J Med Genet 1996;63:209–217.

    Article  PubMed  CAS  Google Scholar 

  60. Loes DJ, Peters C, Krivit W. Globoid cell leukodystrophy: distinguishing early-onset from late-onset disease using a brain MR imaging scoring method. AJNR Am J Neuroradiol 1999;20:316–323.

    PubMed  CAS  Google Scholar 

  61. Jones BV, Barron TF, Towfighi J. Optic nerve enlargement in Krabbe’s disease. AJNR Am J Neuroradiol 1999;20:1228–1231.

    PubMed  CAS  Google Scholar 

  62. Hittmair K, Wimberger D, Wiesbauer P, Zehetmayer M, Budka H. Early infantile form of Krabbe disease with optic hypertrophy: serial MR examinations and autopsy correlation. AJNR Am J Neuroradiol 1994;15:1454–1458.

    PubMed  CAS  Google Scholar 

  63. Vasconcellos E, Smith M. MRI nerve root enhancement in Krabbe disease. Pediatr Neurol 1998;19: 151–152.

    Article  PubMed  CAS  Google Scholar 

  64. Given CA, Santos CC, Durden DD. Intracranial and spinal MR imaging findings associated with Krabbe’s disease: case report. AJNR Am J Neuroradiol 2001;22:1782–1785.

    PubMed  Google Scholar 

  65. Satoh JI, Tokumoto H, Kurohara K, Yukitake M, Matsui M, Kuroda Y, et al. Adult-onset Krabbe disease with homozygous T1853C mutation in the galactocerebrosidase gene. Unusual MRI findings of corticospinal tract demyelination. Neurology 1997;49:1392–1399.

    PubMed  CAS  Google Scholar 

  66. Farina L, Bizzi A, Finocchiaro G, Pareyson D, Sghirlanzoni A, Bertagnolio B, et al. MR imaging and proton MR spectroscopy in adult Krabbe disease. AJNR Am J Neuroradiol 2000;21:1478–1482.

    PubMed  CAS  Google Scholar 

  67. Zarifi MK, Tzika AA, Astrakas LG, Poussaint TY, Anthony DC, Darras BT. Magnetic resonance spectroscopy and magnetic resonance imaging findings in Krabbe’s disease. J Child Neurol 2001;16:522–526.

    Article  PubMed  CAS  Google Scholar 

  68. Brockmann K, Dechent P, Wilken B, Rusch O, Frahm J, Hanefeld F.Proton MRS profile of cerebral metabolic abnormalities in Krabbe disease. Neurology 2003;60:819–825.

    PubMed  CAS  Google Scholar 

  69. Guo AC, Petrella JR, Kurtzberg J, Provenzale JM. Evaluation of white matter anisotropy in Krabbe disease with diffusion tensor MR imaging: initial experience. Radiology 2001;218:809–815.

    PubMed  CAS  Google Scholar 

  70. Sabatelli M, Quaranta L, Madia F, Lippi G, Conte A, Lo Monaco M, et al. Peripheral neuropathy with hypomyelinating features in adultonset Krabbe’s disease. Neuromusc Disord 2002;12:386–391.

    Article  PubMed  CAS  Google Scholar 

  71. Itoh M, Hayashi M, Fujioka Y, Nagashima K, Morimatsu Y, Matsuyama H. Immunohistological study of globoid cell leukodystrophy. Brain Dev 2002;24:284–290.

    Article  PubMed  Google Scholar 

  72. Jatana M, Giri S, Singh AK. Apoptotic positive cells in Krabbe brain and induction of apoptosis in rat C6 glial cells by psychosine. Neurosci Lett 2002;330:183–187.

    Article  PubMed  CAS  Google Scholar 

  73. Krivit W, Shapiro EG, Peters C, Wagner JE, Cornu G, Kurtzberg J, et al. Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med 1998;338:1119–1126.

    Article  PubMed  CAS  Google Scholar 

  74. Argoff CE, Kaneski CR, Blanchette-Mackie EJ, Comly M, Dwyer NK, Brown A, Brady RO, Pentchev PG. Type C Niemann-Pick disease: documentation of abnormal LDL processing in lymphocytes. Biochem Biophys Res Commun 1990; 171:38–45.

    Article  PubMed  CAS  Google Scholar 

  75. Boustany RN, Kaye E, Alroy J. Ultrastructural findings in skin from patients withNiemann-Pick disease, type C. Pediatr Neurol 1990;6:177–183.

    Article  PubMed  CAS  Google Scholar 

  76. Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, et al. Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 1997;277:228–231.

    Article  PubMed  CAS  Google Scholar 

  77. Sylvain M, Arnold DL, Scriver CR, Schreiber R, Shevell MI. Magnetic resonance spectroscopy in Niemann-Pick disease type C: correlation with diagnosis and clinical response to cholestyramine and lovastatin. Pediatr Neurol 1994; 10:228–232.

    Article  PubMed  CAS  Google Scholar 

  78. Palmeri S, Battisti C, Federico A, Guazzi GC. Hypoplasia of the corpus callosum in Niemann-Pick type C disease. Neuroradiology 1994;36:20–22.

    Article  PubMed  CAS  Google Scholar 

  79. Tedeschi G, Bonavita S, Barton NW, Betolino A, Frank JA, Patronas NJ, Alger JR, Schiffmann R. Proton magnetic resonance spectroscopic imaging in the clinical evaluation of patients with Niemann-Pick type C disease. J Neurol Neurosurg Psychiatry 1998;65:72–79.

    PubMed  CAS  Google Scholar 

  80. Grau AJ, Brandt T, Weisbrod M, Niethammer R, Forsting M, Cantz M, Vanier MT, Harzer K.Adult Niemann-Pick disease type C mimicking features of multiple sclerosis. J Neurol Neurosurg Psychiatry 1997; 63:552.

    Article  PubMed  CAS  Google Scholar 

  81. Chen CY, Zimmerman RA, Lee CC, Chen FH, Yuh YS, Hsiao HS. Neuroimaging findings in late infantile GM1 gangliosidosis. AJNR Am J Neuroradiol 1998;19:1628–1630.

    PubMed  CAS  Google Scholar 

  82. Campdelacreu J, Munoz E, Gomez B, Pujol T, Chabas A, Tolosa E. Generalised dystonia with an abnormal magnetic resonance imaging signal in the basal ganglia: a case of adult-onset GM1 gangliosidosis. Mov Disord 2002;17: 1095–1097.

    Article  PubMed  Google Scholar 

  83. Kobayashi O, Takashima S. Thalamic hyperdensity on CT in infantile GM1-gangliosidosis. Brain Dev 1994; 16:472–474.

    Article  PubMed  CAS  Google Scholar 

  84. Mugikura S, Takahashi S, Higano S, Kurihara N, Kon K, Sakamoto K. MR findings in Tay-Sachs disease. J Comput Assist Tomogr 1996;20:551–555.

    Article  PubMed  CAS  Google Scholar 

  85. Nassogne MC, Commare MC, Lellouch-Tubiana A, Emond S, Zerah M, Caillaud C, et al. Unusual presentation of GM2 gangliosidosis mimicking a brain stem tumor in a 3-year-old girl. AJNR Am J Neuroradiol 2003;24:840–842.

    PubMed  Google Scholar 

  86. Alkan A, Kutlu R, Yakinci C, Sigirci A, Aslan M, Sarac K. Infantile Sandhoff’s disease: multivoxel magnetic resonance spectroscopy findings. J Child Neurol 2003;18:425–428.

    Article  PubMed  Google Scholar 

  87. Loes DJ, Hite S, Moser H, Stillman AE, Shapiro E, Lockman L, Latchaw RE, Krivit W. Adrenoleukodystrophy: a scoring method for brain MR observations. AJNR Am J Neuroradiol 1994;15:1761–1766.

    PubMed  CAS  Google Scholar 

  88. Schaumburg HH, Powers JM, Raine CS, Suzuki K, Richardson EP Jr. Adrenoleukodystrophy: a clinical and pathological study of 17 cases. Arch Neurol 1975;32:577–591.

    PubMed  CAS  Google Scholar 

  89. Melhem ER, Breiter SN, Ulug AM, Raymond GV, Moser HW. Improved tissue characterization in adrenoleukodystrophy using magnetization transfer imaging. AJR Am J Roentgenol 1996;166: 689–695.

    PubMed  CAS  Google Scholar 

  90. Ito R, Melhem ER, Mori S, Eichler FS, Raymond GV, Moser HW. Diffusion tensor brain MR imaging in X-linked cerebral adrenoleukodystrophy. Neurology 2001;56:544–547.

    PubMed  CAS  Google Scholar 

  91. Eichler FS, Barker PB, Cox C, Edwin D, Ulug AM, Moser HW, Raymond GV. Proton MR spectroscopic imaging predicts lesion progression on MRI in X-linked adrenoleukodystrophy. Neurology 2002;58:901–907.

    PubMed  CAS  Google Scholar 

  92. Fatemi A, Barker PB, Ulug AM, Nagae-Poetscher LM, Beauchamp NJ, Moser AB, Raymond GV, Moser HW, Naidu S. Neurology 2003;60:1301–1307.

    PubMed  CAS  Google Scholar 

  93. Moser HW. Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain 1997;120: 1485–1508.

    Article  PubMed  Google Scholar 

  94. Powers JM, Moser HW. Peroxisomal disorders: genotype, phenotype, major neuropathologic lesions, and pathogenesis. Brain Pathol 1998;8:101–120.

    Article  PubMed  CAS  Google Scholar 

  95. Senior K. Lorenzo’s oil may help to prevent ALD symptoms. Lancet Neurol 2002;1:468.

    Article  PubMed  Google Scholar 

  96. Moser HW, Kok F, Neumann S, et al. Adrenoleukodystrophy update: genetics and effect of Lorenzo’s oil therapy in asymptomatic patients. Int Pediatr 9 1994;196-204.

    Google Scholar 

  97. Barth PG, Gootjes J, Bode H, Vreken P, Majoie CB, Wanders RJ.Late onset white matter disease in peroxisome biogenesis disorder. Neurology. 2001; 57:1949–1955.

    PubMed  CAS  Google Scholar 

  98. Powers JM, Moser HW. Peroxisomal disorders: genotype, phenotype, major neuropathologic lesions, and pathogenesis. Brain Pathol 1998;8:101–120.

    Article  PubMed  CAS  Google Scholar 

  99. DiMauro S, Schon EA. Mitochondrial respiratory chain diseases. N Engl J Med 2003;348;2656–2668.

    Article  PubMed  CAS  Google Scholar 

  100. Hart PE, DeVivo DC, Schapira AHV. Clinical features of the mitochondrial encephalomyopathies. In: Schapira AHV, DiMauro S, eds. Mitochondrial Disorders in Neurology 2. Boston: Butterworth Heinemann; 2002:35–68.

    Google Scholar 

  101. Schon EA, Bonilla E, DiMauro S. Mitochondrial DNA mutations and pathogenesis. J Bioenerg Biomembr 1997;29:131–149.

    Article  PubMed  CAS  Google Scholar 

  102. Wallace DC. Mitochondrial diseases in mouse and man. Science 1999;283:1482–1488.

    Article  PubMed  CAS  Google Scholar 

  103. Darin N, Oldfors A, Moslemi A-R Holme E, Tulinius M. The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA abnormalities. Ann Neurol 2001;49: 377–383.

    Article  PubMed  CAS  Google Scholar 

  104. Servidei S. Mitochondrial encephalomyopathies: gene mutation. Neuromuscular Disord 1998;8:18–19.

    Google Scholar 

  105. Andreu AL, Hanna MG, Reichmann H, Bruno C, Penn AS, Tanji K, et al. Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA. N Engl J Med 1999;341:1037–1044.

    Article  PubMed  CAS  Google Scholar 

  106. Vissing J, Ravn K, Danielsen ER, Duno M, Wibrand F, Wevers RA, Schwartz M. Multiple mtDNA deletions with features of MNGIE. Neurology 2002;59:926–929.

    PubMed  CAS  Google Scholar 

  107. Rowland LP, Blake DM, Hirano M, DiMauro S, Schon EA, Hays AP, et al. Clinical syndromes associated with ragged red fibers. Rev Neurol 1991;147:467–473.

    PubMed  CAS  Google Scholar 

  108. Barkovich AJ, Good WV, Koch TK, Berg BO. Mitochondrial disorders: analysis of their clinical and imaging characteristics. Am J Neuroradiol 1993;14:1119–1137.

    PubMed  CAS  Google Scholar 

  109. Valanne L, Ketonen L, Majander A, Suomalainen A, Pihko H. Neuroradiologic findings in children with mitochondrial disorders. AJNR Am J Neuroradiol 1998;19:369–367.

    PubMed  CAS  Google Scholar 

  110. Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a distinctive clinical syndrome. Ann Neurol 1984;16:481–488.

    Article  PubMed  CAS  Google Scholar 

  111. Allard JC, Tilak S, Carter AP. CT and MR of MELAS syndrome. Am J Neuroradiol 1988;9:1234–1238.

    PubMed  CAS  Google Scholar 

  112. Ohama E, Ohara S, Ikuta F, Tanaka K, Nishizawa M, Miyatake T. Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy. Acta Neuoropathol 1987;74:226–233.

    Article  CAS  Google Scholar 

  113. Sue CM, Crimmins DS, Soo YS, Pamphlett R, Presgrave CM, Kotsimbos N, Jean-Francois MJ, Byrne E, Morris JG. Neuroradiological features of six kindreds with MELAS tRNALeu A3243G point mutation: implications for pathogenesis. J Neurol Neurosurg Psychiatry 1998;65, 233-240.

    Google Scholar 

  114. Matthews PM, Andermann F, Silver K, Karpati G, Arnold DL. Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial cytopathies. Neurology 1993;43: 2484–2490.

    Google Scholar 

  115. Dubeau F, De Stefano N, Zifkin BG, Arnold DL, Shoubridge EA. Oxidative phosphorylation defect in the brains of carriers of the tRNAleu (UUR) A3242G mutation in a MELAS pedigree. Ann Neurol 2000;47:179–185.

    Article  PubMed  CAS  Google Scholar 

  116. Ishiyama G, Lopez I, Baloh RW, Ishiyama A. Canavan’s leukodystrophy is associated with defects in cochlear neurodevelopment and deafness. Neurology. 2003;60:1702–1704.

    PubMed  Google Scholar 

  117. Feigelman, T, Shih VE, Buyse ML. Prolonged survival in Canavan disease. Dysmorph Clin Genet 1991; 5:107–110.

    Google Scholar 

  118. Hagenfeldt L, Bollgren I, Venizelos N. N-acetylaspartic aciduria due to aspartoacylase deficiency—a new etiology of childhood leukodystrophy. J Inherit Metab Dis 1967;10:135–141.

    Article  Google Scholar 

  119. Kvittingen EA; Guldal G, Borsting S, Skalpe IO, Stokke O, Jellum E. N-acetylaspartic aciduria in a child with a progressive cerebral atrophy. Clin Chim Acta 1986;158:217–227.

    Article  PubMed  CAS  Google Scholar 

  120. Divry P, Vianey-Liaud C, Gay C, Macabeo V, Rapin F, Echenne B. N-acetylaspartic aciduria: report of three new cases in children with a neurological syndrome associating macrocephaly and leucodystrophy. J Inherit Metab Dis 1988;11:307–308..

    Article  PubMed  CAS  Google Scholar 

  121. Matalon R, Michals K, Sebesta D, Deanching M, Gashkoff P, Casanova J. Aspartoacylase deficiency and N-acetylaspartic aciduria in patients with Canavan disease. Am J Med Genet 1988;29:463–471.

    Article  PubMed  CAS  Google Scholar 

  122. Kaul R, Gao GP, Balamurugan K, Matalon R. Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease. Nature Genet. 1993;5:118–123.

    Article  PubMed  CAS  Google Scholar 

  123. Valk J and Van der Knaap MS. Magnetic Resonance of Myelin, Myelination, and Myelin Disorders. New York: Springer Verlag; 1989.

    Google Scholar 

  124. Toft PB, Geiss-Holtorff R, Rolland MO, Pryds O, Muller-Forell W, Christensen E, et al. Magnetic resonance imaging in juvenile Canavan disease. Eur J Pediatr. 1993;152:750–753.

    Article  PubMed  CAS  Google Scholar 

  125. Wittsack HJ, Kugel H, Roth B, Heindel W. Quantitative measurements with localized 1H MR spectroscopy in children with Canavan’s disease. J Magn Reson Imaging 1996;6:889–893.

    Article  PubMed  CAS  Google Scholar 

  126. Janson C, McPhee S, Bilaniuk L, Haselgrove J, Testaiuti M, Freese A, et al. Clinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain. Hum Gene Ther 2002;13:1391–1412.

    Article  PubMed  CAS  Google Scholar 

  127. Biery BJ, Stein DE, Morton DH, Goodman SI. Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish. Am J Hum Genet 1996;59:1006–1011.

    PubMed  CAS  Google Scholar 

  128. Brismar J, Ozand PT. CT and MR of the brain in glutaric acidemia type I: a review of 59 published cases and a report of 5 new patients. AJNR Am J Neuroradiol 1995;16:675–683.

    PubMed  CAS  Google Scholar 

  129. Twomey EL, Naughten ER, Donoghue VB, Ryan S. Neuroimaging findings in glutaric aciduria type 1. Pediatr Radiol 2003;33:823–830.

    Article  PubMed  Google Scholar 

  130. Strauss KA, Morton DH. Type I glutaric aciduria, part 2: a model of acute striatal necrosis. Am J Med Genet 2003;121:53–50.

    Article  Google Scholar 

  131. Moller HE, Weglage J, Bick U, Wiedermann D, Feldmann R, Ullrich K. Brain imaging and proton magnetic resonance spectroscopy in patients with phenylketonuria. Pediatrics 2003;112:1580–1583.

    PubMed  Google Scholar 

  132. Bick U, Fahrendorf G, Ludolph AC, Vassallo P, Weglage J, Ullrich K. Disturbed myelination in patients with treated hyperphenylalaninemia: evaluation with magnetic resonance imaging. Eur J Pediatr 1991;150: 185–195.

    Article  PubMed  CAS  Google Scholar 

  133. Bick U, Ullrich K, Stöber U, et al. White matter abnormalities in patients with treated hyperphenylalaninemia: magnetic resonance relaxometry and proton spectroscopy findings. Eur J Pediatr 1993; 152:1012–1020.

    Article  PubMed  CAS  Google Scholar 

  134. Thomson AJ, Tillotson S, Smith I, Kendall B, Moore SG, Brenton DP. Brain MRI changes in phenylketonuria. Brain 1993;116:811–821.

    Article  Google Scholar 

  135. Leuzzi V, Trasimeni G, Gualdi GF, Antonozzi I. Biochemical, clinical and neuroradiological (MRI) correlations in late-detected PKU patients. J Inherit Metab Dis 1995;18:624–634.

    Article  PubMed  CAS  Google Scholar 

  136. Möller H, Pietz J, Kreis R, Schmidt H, Meyding-Lamadé UK, Rupp A, Boesch C. Phenylketonuria: findings at MR imaging and localized in vivo H-1 MR spectroscopy of the brain in patients with early treatment. Radiology 1996;201:413–420.

    Google Scholar 

  137. Weglage J, Bick U, Wiedermann D, Feldmann R, and Ullrich K. Brain imaging and proton magnetic resonance spectroscopy in patients with phenylketonuria. Pediatrics 2003;112:1150–1583.

    Google Scholar 

  138. Auerbach VH, DiGeorge A. Maple syrup urine disease. In: Hommes FA, Van den Berg CJ, eds. Inborn Errors of Metabolism. London: Academic Press; 1973;337.

    Google Scholar 

  139. Naylor EW. Newborn screening for maple syrup urine disease (branched chain ketoaciduria). In: Bickel H, Guthrie R, Hammersen G, eds. Neonatal Screening for Inborn Errors of Metabolism. Berlin: Springer-Verlag; 1980:19.

    Google Scholar 

  140. Marshall L, DiGeorge A. Maple syrup urine disease in the Old Order Mennonites (abstract). Am J Hum Genet 1981;33:139A.

    Google Scholar 

  141. Jan W, Zimmerman RA, Wang ZJ, Berry GT, Kaplan PB, Kaye EM. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology 2003;45:393–399.

    Article  PubMed  Google Scholar 

  142. Felber SR, Sperl W, Chemelli A, Murr C, Wendel U. Maple syrup urine disease: metabolic decompensation monitored by proton magnetic resonance imaging and spectroscopy. Ann Neurol 1993;33:396–401.

    Article  PubMed  CAS  Google Scholar 

  143. Sener RN. Diffusion magnetic resonance imaging in intermediate form of maple syrup urine disease. J Neuroimaging 2002;12:368–370.

    Article  PubMed  CAS  Google Scholar 

  144. Nagata N, Matsuda I, Oyanagi K. Estimated frequency of urea cycle enzymopathies in Japan. Am J Med Genet 1991;39:228–229.

    Article  PubMed  CAS  Google Scholar 

  145. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969–1996. Pediatrics 2000; 105:e10.

    Article  PubMed  CAS  Google Scholar 

  146. Brusilow SW, Horwich AL. Urea cycle enzymes. In: Scriver CR, Beaudet AL, Valle D, Sly WS, Childs B, Kinzler KW, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001:1909–1964.

    Google Scholar 

  147. Dionisi-Vici C, Rizzo C, Burlina AB, Caruso U, Sabetta G, Uziel G, Abeni D. Inborn errors of metabolism in the Italian pediatric population: a national retrospective survey. J Pediatr 2002;140:321–327.

    Article  PubMed  Google Scholar 

  148. Tuchman M, Jaleel N, Morizono H, Sheehy L, Lynch MG. Mutations and polymorphisms in the human ornithine transcarbamylase gene. Hum Mutat 2002;19:93–107.

    Article  PubMed  CAS  Google Scholar 

  149. McCullough BA, Yudkoff M, Batshaw ML, Wilson JM, Wilson JM, Raper SE, et al. Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype. Am J Med Genet 2000; 93: 313–319.

    Article  PubMed  CAS  Google Scholar 

  150. Campbell AGM, Rosenberg LE, Snodgrass PJ, Nuzum CT. Ornithine transcarbamylase deficiency: a cause of lethal neonatal hyperammonemia in males. N Engl J Med 1973;288:1–6.

    Article  PubMed  CAS  Google Scholar 

  151. Kang ES, Snodgrass PJ, Gerald PS. Ornithine transcarbamylase deficiency in the newborn infant. J Pediatr 1973;82:642–649.

    Article  PubMed  CAS  Google Scholar 

  152. Batshaw ML, Brusilow S, Waber L, Blom W, Brubakk AM, Burton BK, et al. Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion. N Engl J Med 1982; 306:1387–1392.

    Article  PubMed  CAS  Google Scholar 

  153. Rowe PC, Newman SL, Brusilow SW. Natural history of symptomatic partial ornithine transcarbamylase deficiency. N Engl J Med 1986;314:541–547.

    Article  PubMed  CAS  Google Scholar 

  154. Di Magno EP, Lowe JE, Snodgrass PJ, Jones JD. Ornithine transcarbamylase deficiency-a cause of bizarre behavior in a man. N Engl J Med 1986;315:744–747.

    Article  Google Scholar 

  155. Batshaw ML, MacArthur RB, Tuchman M. Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatr 2001;138: S46–S54; discussion S54–S55.

    Article  PubMed  CAS  Google Scholar 

  156. Batshaw ML, Hyman SL, Mellits ED, Thomas GH, DeMuro R, Coyle JT. Behavioral and Neurotransmitter Changes in the Urease-Infused Rat: A model of congenital hyperammonemia. Pediatr Res 1986;20:1310–1315.

    Article  PubMed  CAS  Google Scholar 

  157. Maestri NE, Clissold DMA, Brusilow S. Neonatal onset ornithine transcarbamylase deficiency. J Pediatr 1999;134:268–272.

    Article  PubMed  CAS  Google Scholar 

  158. Maestri NE, Lord C, Glynn M, Bale A, Brusilow SW. The phenotype of ostensibly healthy women who are carriers for ornithine transcarbamylase deficiency. Medicine 1998;77:389–397.

    Article  PubMed  CAS  Google Scholar 

  159. Yudkoff M, Daikhin Y, Nissim I, Jawad A, Wilson J, Batshaw M. In vivo nitrogen metabolism in ornithine transcarbamylase deficiency. J Clini Invest 1996;89:2167–2173.

    Google Scholar 

  160. Tuchman M, Plante RJ, Garcia-Perez MA, Rubio V. Relative frequency of mutations causing ornithine transcarbamylase deficiency in 78 families. Hum Genet 1996;97:274–276.

    Article  PubMed  CAS  Google Scholar 

  161. Kendall BE, Kingsley DPE, Leonard JV, Lingam S, Oberholzer VG. Neurological features and computed tomography of the brain in children with ornithine carbamoyl transferase deficiency. J Neurol, Neurosurg Psychiatry 1983; 46:28–34.

    CAS  Google Scholar 

  162. Msall M, Batshaw ML, Suss R, Brusilow SW, Mellits ED. Neurologic outcome in children with inborn errors of urea synthesis. Outcome of urea-cycle enzymopathies. N Engl J Med 1984;310:1500–1505.

    Article  PubMed  CAS  Google Scholar 

  163. Takayanagi M, Ohtake A, Ogura N, Nakajima H, Hoshino M. A female case of ornithine transcarbamylase deficiency with marked computed tomographic abnormalities of the brain. Brain Dev 1984;6:58–60.

    PubMed  CAS  Google Scholar 

  164. Christodoulou J, Qureshi A, McInnes RR, Clarke JTR. Ornithine transcarbamylase deficiency presenting with strokelike episodes. J Pediatr 1993;122:423–425.

    Article  PubMed  CAS  Google Scholar 

  165. Kurihara K, Takanashi J, Tomita M, Kobayashi K, et al. (2003) Magnetic resonance imagine in late onset ornithine transcarbamylase deficiency. Brain Dev 25:40–44.

    Google Scholar 

  166. Fitzgerald SM, Hetherington HP, Behar KL, Shulman RG. Effects of acute hyperammonemia on cerebral amino acid metabolism and pH, in vivo, measured by 1H and 31P nuclear magnetic resonance. J Neurochem 1989;52: 741–749.

    Article  Google Scholar 

  167. Bates TE, Williams SR, Kauppinen RA, Gadian DG. Observations of cerebral metabolites in an animal model of acute liver failure. J Neurochem 1989;53:102–110.

    Article  PubMed  CAS  Google Scholar 

  168. Batshaw ML, Roan Y, Jung AL, Rosenberg LA, Brusilow SW. Cerebral dysfunction in asymptomatic carriers of ornithine transcarbamylase deficiency. N Engl J Med 1980;302:482–485.

    Article  PubMed  CAS  Google Scholar 

  169. Connelly A, Cross JH, Gadian DG, Hunter JV, Kirkham FJ, Leonard JV. Magnetic Resonance Spectroscopy Shows increased Brain glutamine in ornithine carbamoyl transferase deficiency. Pediatr Res 1993;33:77–81.

    Article  PubMed  CAS  Google Scholar 

  170. Krieger I, Snodgrass PJ, Roskamp J. Atypical clinical case of ornithine transcarbamylase deficiency due to a new (comparison with Reye’s disease). J Clin Endrocrinol Med 1979;388-392.

    Google Scholar 

  171. Kornfeld M, Woodfin BM, Papile L, Davis LE, Bernard LR. Neuropathy of Ornithine Carbamoyl Transferase Deficiency. Acta Neuropathol (Berl) 1985;65:261–264.

    Article  CAS  Google Scholar 

  172. Dolman CL, Clasen RA, Dorovini-Zis K. Severe Cerebral damage in ornithine transcarbamylase deficiency. Clin Neuropathol 1988;7:10–15.

    PubMed  CAS  Google Scholar 

  173. Yamanouchi H, Yokoo H, Yuharea Y, Marayama K, Sasaki A, Hirato J, Nakazato Y. An Autopsy case of ornithine transcarbamylase deficiency. Brain Dev 2002;24:91–94.

    Article  PubMed  Google Scholar 

  174. Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, et al. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell 1998; 2:223–232.

    Article  PubMed  CAS  Google Scholar 

  175. Bootsma D, et al. Nucleotide excision repair syndromes: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. In: Vogelstein B, Kinzler KW, eds. The Genetic Basis of Human Cancer. 2nd ed. New York: McGraw-Hill; 2002.

    Google Scholar 

  176. Kraemer KH, Slor H Xeroderma pigmentosum. Clin Dermatol 1985;3:33–69.

    Article  PubMed  CAS  Google Scholar 

  177. Kraemer KH, Lee MM, Andrews AD, Lambert WC. The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm. Arch Dermatol 1994; 130:1018–1021.

    Article  PubMed  CAS  Google Scholar 

  178. Rapin I, Lindenbaum Y, Dickson DW, Kraemer KH, Robbins JH. Cockayne syndrome and xeroderma pigmentosum. Neurology 2000;55:1442–1449.

    PubMed  CAS  Google Scholar 

  179. Roytta M, Anttinen A. Xeroderma pigmentosum with neurological abnormalities. A clinical and neuropathological study. Acta Neurol Scand 1986;73:191–199.

    PubMed  CAS  Google Scholar 

  180. Kanda T, Oda M, Yonezawa M, Tamagawa K, Isa F, Hanakago R, Tsukagoshi H. Peripheral neuropathy in xeroderma pigmentosum. Brain 1990;113:1025–1044.

    Article  PubMed  Google Scholar 

  181. Mimaki T, Itoh N, Abe J, Tagawa T, Sato K, Yabuuchi H, Takebe H. Neurological manifestations in xeroderma pigmentosum. Ann Neurol 1986;20:70–75.

    Article  PubMed  CAS  Google Scholar 

  182. Mimaki T, Tagawa T, Tanaka J, Sato K, Yabuuchi H. EEG and CT abnormalities in xeroderma pigmentosum. Acta Neurol Scand 1989;80:136–141.

    PubMed  CAS  Google Scholar 

  183. Sugita K, Takanashi J, Ishii M, Niimi H. Comparison of MRI white matter changes with neuropsychologic impairment in Cockayne syndrome. Pediatr Neurol 1992;8:295–298.

    Article  PubMed  CAS  Google Scholar 

  184. Battistella PA, Peserico A. Central nervous system dysmyelination in PIBI(D)S syndrome: a further case. Childs Nerv Syst 1996;12:110–113.

    Article  PubMed  CAS  Google Scholar 

  185. Hakamada S, Watanabe K, Sobue G, Hara K, Miyazaki S. Xeroderma pigmentosum: neurological, neurophysiological and morphological studies. Eur Neurol 1982;21:69–76.

    PubMed  CAS  Google Scholar 

  186. Origuchi Y, Eda I, Matsumoto S, Furuse A. Quantitative histologic study of sural nerves in xeroderma pigmentosum. Pediatr Neurol 1987;3:356–359.

    Article  PubMed  CAS  Google Scholar 

  187. Lindenbaum Y, Dickson D, Rosenbaum P, Kraemer K, Robbins I, Rapin I. Xeroderma pigmentosum/cockayne syndrome complex: first neuropathological study and review of eight other cases. Eur J Paediatr Neurol 2001;5: 225–242.

    Article  PubMed  CAS  Google Scholar 

  188. Stojkovic T, Defebvre L, Quilliet X, Eveno E, Sarasin A, Mezzina M, Destee A. Neurological manifestations in two related xeroderma pigmentosum group D patients: complications of the late-onset type of the juvenile form. Mov Disord 1997;12:616–619.

    Article  PubMed  CAS  Google Scholar 

  189. Bassuk AG, Joshi A, Burton BK, Larsen MB, Burrowes DM, Stack C. Alexander disease with serial MRS and a new mutation in the glial fibrillary acidic protein gene. Neurology 2003 61:1014–1015.

    PubMed  CAS  Google Scholar 

  190. Springer S, Erlewein R, Naegele T, Becker I, Auer D, Grodd W, Krageloh-Mann I. Alexander disease—classification revisited and isolation of a neonatal form. Neuropediatrics 2000;31:86–92.

    Article  PubMed  CAS  Google Scholar 

  191. Namekawa M, Takiyama Y, Aoki Y, Takayashiki N, Sakoe K, Shimazaki H, et al. Identification of GFAP gene mutation in hereditary adult-onset Alexander’s disease. Ann Neurol 2002;52:779–785.

    Article  PubMed  CAS  Google Scholar 

  192. Martidis A, Yee RD, Azzarelli B, Biller J.Neuro-ophthalmic, radiographic, and pathologic manifestations of adult-onset Alexander disease. Arch Ophthalmol 1999;117:265–267.

    PubMed  CAS  Google Scholar 

  193. Stumpf E, Masson H, Duquette A, Berthelet F, McNabb J, Lortie A, et al. Adult Alexander disease with autosomal dominant transmission: a distinct entity caused by mutation in the glial fibrillary acid protein gene. Arch Neurol 2003;60:1307–1312.

    Article  PubMed  Google Scholar 

  194. Brockmann K, Meins M, Taubert A, Trappe R, Grond M, Hanefeld F. A novel GFAP mutation and disseminated white matter lesions: adult Alexander disease? Eur Neurol 2003;50:100–105.

    Article  PubMed  Google Scholar 

  195. Kinoshita T, Imaizumi T, Miura Y, Fujimoto H, Ayabe M, Shoji H, et al. A case of adult-onset Alexander disease with Arg416Trp human glial fibrillary acidic protein gene mutation. Neurosci Lett 2003;350: 169–172.

    Article  PubMed  CAS  Google Scholar 

  196. Gordon N. Alexander disease. Eur J Paediatr Neurol 2003;7:395–399.

    Article  PubMed  Google Scholar 

  197. Johnson AB, Brenner M. Alexander’s disease: clinical, pathologic, and genetic features. J Child Neurol. 2003;18:625–632.

    Article  PubMed  Google Scholar 

  198. Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A. Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 2001;27:117–120.

    Article  PubMed  CAS  Google Scholar 

  199. Namekawa M, Takiyama Y, Aoki Y, Takayashiki N, Sakoe K, Shimazaki H, et al. Identification of GFAP gene mutation in hereditary adult-onset Alexander’s disease. Ann Neurol 2002;52:779–785.

    Article  PubMed  CAS  Google Scholar 

  200. Meins M, Brockmann K, Yadav S, Haupt M, Sperner J, Stephani U, Hanefeld F.Infantile Alexander disease: a GFAP mutation in monozygotic twins and novel mutations in two other patients. Neuropediatrics 2002;33: 194–198.

    Article  PubMed  CAS  Google Scholar 

  201. van der Knaap MS, Naidu S, Breiter SN, Blaser S, Stroink H, Springer S, et al. Alexander disease: diagnosis with MR imaging. AJNR Am J Neuroradiol 2001;22:541–552.

    PubMed  Google Scholar 

  202. Stumpf E, Masson H, Duquette A, Berthelet F, McNabb J, Lortie A, et al. Adult Alexander disease with autosomal dominant transmission: a distinct entity caused by mutation in the glial fibrillary acid protein gene. Arch Neurol 2003;60:1307–1312.

    Article  PubMed  Google Scholar 

  203. Gorospe JR, Naidu S, Johnson AB, Puri V, Raymond GV, Jenkins SD, et al. Molecular findings in symptomatic and pre-symptomatic Alexander disease patients. Neurology 2002;58:1494–1500.

    PubMed  CAS  Google Scholar 

  204. Guthrie SO, Burton EM, Knowles P, Marshall R. Alexander’s disease in a neurologically normal child: a case report. Pediatr Radiol 2003;33:47–49.

    Article  PubMed  Google Scholar 

  205. Imamura A, Orii KE, Mizuno S, Hoshi H, Kondo T. MR imaging and 1H-MR spectroscopy in a case of juvenile Alexander disease. Brain Dev 2002;24:723–726.

    Article  PubMed  Google Scholar 

  206. Sawaishi Y, Hatazawa J, Ochi N, Hirono H, Yano T, Watanabe Y, Okudera T, Takada G. Positron emission tomography in juvenile Alexander disease. J Neurol Sci 1999;165:116–120.

    Article  PubMed  CAS  Google Scholar 

  207. Li R, Messing A, Goldman JE, Brenner M. GFAP mutations in Alexander disease. Int J Dev Neurosci 2002;20:259–268.

    Article  PubMed  Google Scholar 

  208. Messing A, Goldman JE, Johnson AB, Brenner M. Alexander disease: new insights from genetics. J Neuropathol Exp Neurol 2001;60:563–573.

    PubMed  CAS  Google Scholar 

  209. Mignot C, Boespflug-Tanguy O, Gelot A, Dautigny A, Pham-Dinh D, Rodriguez D.Alexander disease: putative mechanisms of an astrocytic encephalopathy. Cell Mol Life Sci 2004;61:369–385.

    Article  PubMed  CAS  Google Scholar 

  210. Hanefeld F, Holzbach U, Kruse B, Wilichowski E, Christen HJ, Frahm J. Diffuse white matter disease in three children: an encephalopathy with unique features on magnetic resonance imaging and proton magnetic resonance spectroscopy. Neuropediatrics 1993;24: 244–248.

    PubMed  CAS  Google Scholar 

  211. van der Knaap MS, Barth PG, Gabreels FJ, Franzoni E, Begeer JH, Stroink H, Rotteveel JJ, Valk J. A new leukoencephalopathy with vanishing white matter. Neurology 1997;48:845–855.

    PubMed  Google Scholar 

  212. Schiffmann R, Moller JR, Trapp BD, Shih HHL, Farrer RG, Katz DA, et al. Childhood ataxia with diffuse central nervous system hypomyelination. Ann. Neurol 1994;35:331–340..

    Article  PubMed  CAS  Google Scholar 

  213. van der Knaap MS, Kamphorst W, Barth PG, Kraaijeveld CL, Gut E, Valk J. Phenotypic variation in leukoencephalopathy with vanishing white matter. Neurology 1998;51:540–547.

    PubMed  Google Scholar 

  214. Sugiura C, Miyata H, Oka A, Takashima S, Ohama E, Takeshita K. A Japanese girl with leukoencephalopathy with vanishing white matter. Brain Dev 2001;23:58–61.

    Article  PubMed  CAS  Google Scholar 

  215. Topcu M, Saatci I, Apak RA, Soylemezoglu F. A case of leukoencephalopathy with vanishing white matter. Neuropediatrics 2000;31:100–103.

    Article  PubMed  CAS  Google Scholar 

  216. Rosemberg S, Leite Cda C, Arita FN, Kliemann SE, Lacerda MT. Leukoencephalopathy with vanishing white matter: report of four cases from three unrelated Brazilian families. Brain Dev 2002;24:250–256.

    Article  PubMed  Google Scholar 

  217. Francalanci P, Eymard-Pierre E, Dionisi-Vici C, Boldrini R, Piemonte F, Virgili R, et al. Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to chromosome 3q27. Neurology 2001;57: 265–270.

    PubMed  CAS  Google Scholar 

  218. Fogli A, Dionisi-Vici C, Deodato F, Bartuli A, Boespflug-Tanguy O, Bertini E. A severe variant of childhood ataxia with central hypomyelination/vanishing white matter leukoencephalopathy related to EIF21B5 mutation. Neurology 2002;59:1966–1968.

    PubMed  CAS  Google Scholar 

  219. Boltshauser E, Barth PG, Troost D, Martin E, Stallmach T. Vanishing white matter” and ovarian dysgenesis in an infant with cerebrooculo-facio-skeletal phenotype. Neuropediatrics 2002;33:57–62.

    Article  PubMed  CAS  Google Scholar 

  220. van der Knaap MS, Van Berkel CG, Herms J, Van Coster R, Baethmann M, Naidu S, et al. eIF2B-related disorders: antenatal onset and involvement of multiple organs. Am J Hum Genet 2003;73: 1199–1207.

    Article  PubMed  Google Scholar 

  221. van der Knaap MS, Kamphorst W, Barth PG, Kraaijeveld CL, Gut E, Valk J. Phenotypic variation in leukoencephalopathy with vanishing white matter. Neurology 1998;51:540–547.

    PubMed  Google Scholar 

  222. Prass K, Bruck W, Schroder NW, Bender A, Prass M, Wolf T, et al. Adult-onset Leukoencephalopathy with vanishing white matter presenting with dementia. Ann Neurol 2001;50:665–668.

    Article  PubMed  CAS  Google Scholar 

  223. Fogli A, Rodriguez D, Eymard-Pierre E, Bouhour F, Labauge P, Meaney BF, et al. Ovarian failure related to eukaryotic initiation factor 2B mutations. Am J Hum Genet 2003;72:1544–1550.

    Article  PubMed  CAS  Google Scholar 

  224. Verghese J, Weidenheim K, Malik S, Rapin I. Adult onset pigmentary orthochromatic leukodystrophy with ovarian dysgenesis. Eur J Neurol 2002;9:663–670.

    Article  PubMed  CAS  Google Scholar 

  225. van der Knaap MS, Wevers RA, Kure S, Gabreels FJ, Verhoeven NM, van Raaij-Selten B, et al. Increased cerebrospinal fluid glycine: a biochemical marker for a leukoencephalopathy with vanishing white matter. Ann Neurol 1999; 14:728–731.

    Google Scholar 

  226. Leegwater PA, Konst AA, Kuyt B, Sandkuijl LA, Naidu S, Oudejans CB, et al. The gene for leukoencephalopathy with vanishing white matter is located on chromosome 3q27. J Hum Genet 1999;65:728–734.

    Article  CAS  Google Scholar 

  227. Francalanci P, Eymard-Pierre E, Dionisi-Vici C, Boldrini R, Piemonte F, Virgili R, et al. Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to chromosome 3q27. Neurology 2001;57: 265–270.

    PubMed  CAS  Google Scholar 

  228. van der Knaap MS, Leegwater PA, Konst AA, Visser A, Naidu S, Oudejans CB, et al. Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter. Ann Neurol 2002;51:264–270.

    Article  PubMed  CAS  Google Scholar 

  229. Topcu M, Saatci I, Apak RA, Soylemezoglu F. A case of leukoencephalopathy with vanishing white matter. Neuropediatrics 2000;31:100–103.

    Article  PubMed  CAS  Google Scholar 

  230. Rosemberg S, Leite Cda C, Arita FN, Kliemann SE, Lacerda MT. Leukoencephalopathy with vanishing white matter: report of four cases from three unrelated Brazilian families. Brain Dev 2002;24:250–256.

    Article  PubMed  Google Scholar 

  231. Fogli A, Rodriguez D, Eymard-Pierre E, Bouhour F, Labauge P, Meaney BF, et al. Ovarian failure related to eukaryotic initiation factor 2B mutations. Am J Hum Genet 2003;72:1544–1550.

    Article  PubMed  CAS  Google Scholar 

  232. Tedeschi, G, Schiffmann R, Barton NW, Shih HHL, Gospe SM Jr, Brady RO, et al Proton magnetic resonance spectroscopic imaging in childhood ataxia with diffuse central nervous system hypomyelination. Neurology 1995; 45:1526–1532.

    PubMed  CAS  Google Scholar 

  233. Schiffmann R, Moller JR, Trapp BD, Shih HHL, Farrer RG, Katz DA, et al. Childhood ataxia with diffuse central nervous system hypomyelination. Ann Neurol 1994;35:331–340.

    Article  PubMed  CAS  Google Scholar 

  234. Bluml S, Philippart M, Schiffmann R, Seymour K, Ross BD. Membrane phospholipids and high-energy metabolites in childhood ataxia with CNS hypomyelination. Neurology 2003;61:648–654.

    PubMed  CAS  Google Scholar 

  235. Gallo A, Rocca MA, Falini A, Scaglione C, Salvi F, Gambini A, et al. Multiparametric MRI in a patient with adult-onset leukoencephalopathy with vanishing white matter. Neurology 2004;62:323–326.

    PubMed  CAS  Google Scholar 

  236. Sugiura C, Miyata H, Oka A, Takashima S, Ohama E, Takeshita K. A Japanese girl with leukoencephalopathy with vanishing white matter. Brain Dev 2001;23:58–61.

    Article  PubMed  CAS  Google Scholar 

  237. Francalanci P, Eymard-Pierre E, Dionisi-Vici C, Boldrini R, Piemonte F, Virgili R, et al. Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to chromosome 3q27. Neurology 2001;57: 265–270.

    PubMed  CAS  Google Scholar 

  238. Bruck W, Herms J, Brockmann K, Schulz-Schaeffer W, Hanefeld F. Myelinopathia centralis diffusa (vanishing white matter disease): evidence of apoptotic oligodendrocyte degeneration in early lesion development. Ann Neurol 2001;50:532–536.

    Article  PubMed  CAS  Google Scholar 

  239. Kaye EM, Doll RF, Natowicz MR, Smith FI. Pelizaeus-Merzbacher disease presenting as spinal muscular atrophy: clinical and molecular studies. Ann Neurol 1994;36:916–919.

    Article  PubMed  CAS  Google Scholar 

  240. Ziereisen F, Dan B, Christiaens F, Deltenre P, Boutemy R, Christophe C. Connatal Pelizaeus-Merzbacher disease in two girls. Pediatr Radiol 2000;30:435–438.

    Article  PubMed  CAS  Google Scholar 

  241. Mimault C, Giraud G, Courtois V, Cailloux F, Boire JY, Dastugue B, et al. Proteolipoprotein gene analysis in 82 patients with sporadic Pelizaeus-Merzbacher Disease: duplications, the major cause of the disease, originate more frequently in male germ cells, but point mutations do not. The Clinical European Network on Brain Dysmyelinating Disease. Am J Hum Genet. 1999;65:360–369.

    Article  PubMed  CAS  Google Scholar 

  242. Cailloux F, Gauthier-Barichard F, Mimault C, Isabelle V, Courtois V, Giraud G, et al. Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating Disease. Eur J Hum Genet. 2000;8:837–845.

    Article  PubMed  CAS  Google Scholar 

  243. Boespflug-Tanguy O, Mimault C, Melki J, Cavagna A, Giraud G, Pham Dinh D, et al. Genetic homogeneity of Pelizaeus-Merzbacher disease: tight linkage to the proteolipoprotein locus in 16 affected families. PMD Clinical Group. Am J Hum Genet. 1994;55:461–467.

    PubMed  CAS  Google Scholar 

  244. Hobson GM, Davis AP, Stowell NC, Kolodny EH, Sistermans EA, de Coo IF, et al. Mutations in noncoding regions of the proteolipid protein gene in Pelizaeus-Merzbacher disease. Neurolog. 2000;55: 1089–1096.

    CAS  Google Scholar 

  245. Statz A, Boltshauser E, Schinzel A, Spiess H. Computed tomography in Pelizaeus-Merzbacher disease. Neuroradiology. 1981;22: 103–105

    Article  PubMed  CAS  Google Scholar 

  246. Plecko B, Stockler-Ipsiroglu S, Gruber S, Mlynarik V, Moser E, Simbrunner J, et al. Degree of hypomyelination and magnetic resonance spectroscopy findings in patients with Pelizaeus Merzbacher phenotype. Neuropediatrics 2003;34:127–136.

    Article  PubMed  CAS  Google Scholar 

  247. Wang PJ, Young C, Liu HM, Chang YC, Shen YZ. Neurophysiologic studies and MRI in Pelizaeus-Merzbacher disease: comparison of classic and connatal forms. Pediatr Neurol 1995;12:47–53.

    Article  PubMed  CAS  Google Scholar 

  248. Ono J, Harada K, Sakurai K, Kodaka R, Shimidzu N, Tanaka J, et al. MR diffusion imaging in Pelizaeus-Merzbacher disease. Brain Dev. 1994;16:219–223.

    Article  PubMed  CAS  Google Scholar 

  249. 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.

    PubMed  Google Scholar 

  250. 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.

    PubMed  CAS  Google Scholar 

  251. Spalice A, Popolizio T, Parisi P, Scarabino T, Iannetti P. Proton MR spectroscopy in connatal Pelizaeus-Merzbacher disease. Pediatr Radiol 2000;30:171–175.

    Article  PubMed  CAS  Google Scholar 

  252. Sasaki A, Miyanaga M, Ototsuji M, et al. Two autopsy cases with Pelizaeus-Merzbacher disease phenotype of adult onset, without mutation of proteolipid protein gene. Acta Neuropathol (Berl) 2000;99:7–13.

    Article  CAS  Google Scholar 

  253. Rizzo WB, Dammann AL, Craft DA. Sjögren-Larsson syndrome: impaired fatty alcohol oxidation in cultured fibroblasts due to deficient fatty alcohol:nicotinamide adenine dinucleotide oxidoreductase activity. J Clin Invest 1988;81:738–744.

    Article  PubMed  CAS  Google Scholar 

  254. Rizzo WB, Dammann AL, Craft DA, Black SH, Henderson Tilton A, Africk D, et al. Sjögren-Larsson syndrome: inherited defect in the fatty alcohol cycle. J. Pediat. 1989;115:228–234.

    Article  PubMed  CAS  Google Scholar 

  255. Tabsh K, Rizzo WB, Holbrook K, Theroux N. Sjögren-Larsson syndrome: technique and timing of prenatal diagnosis. Obstet Gynecol 1993;82:700–703.

    Article  PubMed  CAS  Google Scholar 

  256. Rizzo WB, Craft DA, Kelson TL, Bonnefont JP, Saudubray JM, Schulman JD, et al. Prenatal diagnosis of Sjögren-Larsson syndrome using enzymatic methods. Prenat Diagn 1994;14:577–581.

    Article  PubMed  CAS  Google Scholar 

  257. De Laurenzi V, Rogers GR, Hamrock DJ, Marekov LN, Steinert PM, Compton JG, et al. Sjögren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene. Nat Genet 1996; 12:52–57.

    Article  PubMed  Google Scholar 

  258. van Domburg PH, Willemsen MA, Rotteveel JJ, de Jong JG, Thijssen HO, Heerschap A, et al. Sjö gren-Larsson syndrome: clinical and MRI/MRS findings in FALDH-deficient patients. Neurology 1999;52: 1345–1352.

    PubMed  Google Scholar 

  259. Van Mieghem F, Van Goethem JW, Parizel PM, van den Hauwe L, Cras P, De Meirleire J, et al. MR of the brain in Sjögren-Larsson syndrome. AJNR Am J Neuroradiol 1997;18:1561–1563.

    PubMed  Google Scholar 

  260. Willemsen MA, Lutt MA, Steijlen PM, Cruysberg JR, van der Graaf M, Nijhuis-van der Sanden MW, et al. Clinical and biochemical effects of zileuton in patients with the Sjögren-Larsson syndrome. Eur J Pediatr 2001a;160:711–717.

    PubMed  CAS  Google Scholar 

  261. Mano T, Ono J, Kaminaga T, Imai K, Sakurai K, Harada K, et al. Proton MR spectroscopy of Sjö gren-Larsson’s syndrome. AJNR Am J Neuroradiol 1999;20:1671–1673.

    PubMed  CAS  Google Scholar 

  262. Miyanomae Y, Ochi M, Yoshioka H, Takaya K, Kizaki Z, Inoue F, et al. Cerebral MRI and spectroscopy in Sjögren-Larsson syndrome: case report. Neuroradiology 1995;37:225–228.

    Article  PubMed  CAS  Google Scholar 

  263. Kaminaga T, Mano T, Ono J, Kusuoka H, Nakamura H, Nishimura T. Proton magnetic resonance spectroscopy of Sjö gren-Larsson syndrome heterozygotes. Magn Reson Med 2001;45:1112–1115.

    Article  PubMed  CAS  Google Scholar 

  264. Willemsen MA, IJlst L, Steijlen PM, Rotteveel JJ, de Jong JG, van Domburg PH, et al. Clinical, biochemical and molecular genetic characteristics of 19 patients with the Sjögren-Larsson syndrome. Brain 2001b;124:1426–1437.

    Article  PubMed  CAS  Google Scholar 

  265. Yamaguchi K, Handa T. Sjögren-Larsson syndrome: postmortem brain abnormalities. Pediatr Neurol 1998;18:338–341.

    Article  PubMed  CAS  Google Scholar 

  266. Philpot J, Sewry C, Pennock J, Dubowitz V. Clinical phenotype in congenital muscular dystrophy: correlation with expression of merosin in skeletal muscle. Neuromusc Disord 1995;5:301–305.

    Article  PubMed  CAS  Google Scholar 

  267. Hayashi YK, Koga R, Tsukahara T, Ishii H, Matsuishi T, Yamashita Y, Nonaka I, Arahata K. Deficiency of laminin alpha 2-chain mRNA in muscle in a patient with merosin negative congenital muscular dystrophy. Muscle Nerve 1995;18:1027–1030.

    Article  PubMed  CAS  Google Scholar 

  268. North KN, Specht K, Sethi RK, Shapiro F, Beggs AH. Congenital muscular dystrophy associated with merosin deficiency. J Child Neurol 1996;11:291–295.

    PubMed  CAS  Google Scholar 

  269. Naom I, D’Alessandro M, Topaloglu H, Sewry C, Ferlini A, Helbling Leclerc A, et al. Refinement of the laminin alpha 2 locus to human chromosome 6q2 in severe and mild merosin deficient congenital muscular dystrophy. J Med Genet 1997;34:99–104.

    PubMed  CAS  Google Scholar 

  270. Farina L, Morandi L, Milanesi I, Ciceri E, Mora M, Moroni I, et al. Congenital muscular dystrophy with merosin deficiency: MRI findings in five patients. Neuroradiology 1998;40:807–811.

    Article  PubMed  CAS  Google Scholar 

  271. Morandi L, Di Blasi C, Farina L, Sorokin L, Uziel G, Azan G, et al. Clinical correlations in 16 patients with total or partial laminin alpha2 deficiency characterized using antibodies against 2 fragments of the protein. Arch Neurol 1999;56:209–215.

    Article  PubMed  CAS  Google Scholar 

  272. Tan E, Topaloglu H, Sewry C, Zorlu Y, Naom I, Erdem S, et al. Late onset muscular dystrophy with cerebral white matter changes due to partial merosin deficiency. Neuromusc Disord 1997;7:85–89.

    Article  PubMed  CAS  Google Scholar 

  273. Naom I, D’Alessandro M, Sewry CA, Philpot J, Manzur AY, Dubowitz V, Muntoni F. Laminin alpha 2-chain gene mutations in two siblings presenting with limb-girdle muscular dystrophy. Neuromusc Disord 1998;8: 495–501.

    Article  PubMed  CAS  Google Scholar 

  274. Dubowitz V. 50th ENMC International Workshop: Congenital Muscular Dystrophy, 28 February to 2 March 1997, Naarden, The Netherlands. Neuromusc Disord 1997;7:539–547.

    PubMed  CAS  Google Scholar 

  275. Di Blasi C, Mora M, Pareyson D, Farina L, Sghirlanzoni A, Vignier N, et al. Partial laminin alpha 2 deficiency in a patient with a myopathy resembling inclusion body myositis. Ann Neurol 2000;47:811–816.

    Article  PubMed  Google Scholar 

  276. Cohn RD, Herrmann R, Sorokin L, Wewer UM, Voit T. Laminin alpha2 chain-deficient congenital muscular dystrophy: variable epitope expression in severe and mild cases. Neurology 1998;51:94–100.

    PubMed  CAS  Google Scholar 

  277. Mercuri E, Muntoni F, Berardinelli A, Pennock J, Sewry C, Philpot J, Dubowitz V. Somatosensory and visual evoked potentials in congenital muscular dystrophy: correlation with MRI changes and muscle merosin status. Neuropediatrics 1995;26:3–7.

    PubMed  CAS  Google Scholar 

  278. Mercuri E, Dubowitz L, Berardinelli A, Pennock J, Jongmans M, Henderson S, et al. Minor neurological and perceptuo-motor deficits in children with congenital muscular dystrophy: correlation with brain MRI changes. Neuropediatrics 1995;26:156–162.

    PubMed  CAS  Google Scholar 

  279. Shorer Z, Philpot J, Muntoni F, Sewry C, Dubowitz V. Demyelinating peripheral neuropathy in merosin-deficient congenital muscular dystrophy. J Child Neurol 1995;10:472–475.

    PubMed  CAS  Google Scholar 

  280. Mecuri E, Pennock J, Goodwin F, Sewry C, Cowan F, Dubowitz L, Dubowitz V, Muntoni F. Sequential study of central and peripheral nervous system involvement in an infant with merosin deficient congenital muscular dystrophy. Neuromusc Disord 1996;6:425–429.

    Article  Google Scholar 

  281. Cil E, Topaloglu H, Caglar M, Ozme S. Left ventricular structure and function by echocardiography in congenital muscular dystrophy. Brain Dev 1994;16:301–303.

    Article  PubMed  CAS  Google Scholar 

  282. Spyrou N, Philpot J, Foale R, Camici PG, Muntoni F. Evidence of left ventricular dysfunction in children with merosin-deficient congenital muscular dystrophy. Am Heart J 1998;136:474–476.

    Article  PubMed  CAS  Google Scholar 

  283. Helbling-Leclerc A, Zhang X, Topaloglu H, Cruaud C, Tesson F, Weissenbach J, et al. Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Nat Genet 1995;11: 216–218.

    Article  PubMed  CAS  Google Scholar 

  284. Helbling-Leclerc A, Zhang X, Topaloglu H, Cruaud C, Tesson F, Weissenbach J, et al. Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Nat Genet 1995;11: 216–218.

    Article  PubMed  CAS  Google Scholar 

  285. Helbling-Leclerc A, Zhang X, Topaloglu H, Cruaud C, Tesson F, Weissenbach J, et al. Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Nat Genet 1995;11: 216–218.

    Article  PubMed  CAS  Google Scholar 

  286. Brett FM, Costigan D, Farrell MA, Heaphy P, Thornton J, King MD. Merosin-deficient congenital muscular dystrophy and cortical dysplasia. Eur J Paediatr Neurol 1998;2:77–82.

    Article  PubMed  CAS  Google Scholar 

  287. Mackay MT, Kornberg AJ, Shield L, Phelan E, Kean MJ, Coleman LT, Dennett X. Congenital muscular dystrophy, white-matter abnormalities, and neuronal migration disorders: the expanding concept. J Child Neurol 1998; 13: 481–487.

    PubMed  CAS  Google Scholar 

  288. Pini L, Merlini FMS, Tome M, Chevallay, Gobbi G. Merosin-negative congenital muscular dystrophy, occipital epilepsy with periodic spasms and focal cortical dysplasia. Report of three Italian cases in two families. Brain Dev 1996;18:316–322.

    Article  PubMed  CAS  Google Scholar 

  289. Sunada Y, Edgar TS, Lotz BP, Rust RS, Campbell KP. Merosinnegative congenital muscular dystrophy associated with extensive brain abnormalities. Neurology 1995;45:2084–2089.

    PubMed  CAS  Google Scholar 

  290. Van der Knaap MS, Smit LME, Barth PG Catsman-Berrevoets CE, Brouwer OF, Begeer JH, de Coo IF, Valk J. Magnetic resonance imaging in classification of congenital muscular dystrophies with brain abnormalities. Ann Neurol 1997;42:50–59.

    Article  PubMed  Google Scholar 

  291. Porter FD. Human malformation syndromes due to inborn errors of cholesterol synthesis. Curr Opin Pediatr 2003;15:607–613.

    Article  PubMed  Google Scholar 

  292. Kelley RI. Diagnosis of Smith-Lemli-Opitz syndrome by gas chromatography/mass spectrometry of 7-dehydrocholesterol in plasma, amniotic fluid and cultured skin fibroblasts. Clin Chim Acta 1995;236: 45–58.

    Article  PubMed  CAS  Google Scholar 

  293. Trasimeni G, Di Biasi C, Iannilli M, Orlandi L, Boscherini B, Balducci R, Gualdi GF. MRI in Smith-Lemli-Opitz syndrome type I. Childs Nerv Syst 1997;13:47–49.

    Article  PubMed  CAS  Google Scholar 

  294. Caruso PA, Poussaint TY, Tzika AA, Zurakowski D, Astrakas LG, Elias ER, et al. MRI and (1)H MRS findings in Smith-Lemli-Opitz syndrome. Neuroradiology 2004;46:3–14.

    Article  PubMed  CAS  Google Scholar 

  295. van der Knaap MS, Barth PG, Stroink H, van Nieuwenhuizen O, Arts WF, Hoogenraad F, et al. Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children. Ann Neurol 1995; 37:324–334.

    Article  PubMed  Google Scholar 

  296. Bugiani M, Moroni I, Bizzi A, Nardocci N, Bettecken T, Gartner J, et al. Consciousness disturbances in megalencephalic leukoencephalopathy with subcortical cysts. Neuropediatrics 2003;34:211–214.

    Article  PubMed  CAS  Google Scholar 

  297. Higuchi Y, Hattori H, Tsuji M, Asato R, Nakahata T. Partial seizures in leukoencephalopathy with swelling and a discrepantly mild clinical course. Brain Dev. 2000;22:387–389.

    Article  PubMed  CAS  Google Scholar 

  298. Topcu M, Gartioux C, Ribierre F, Yalcinkaya C, Tokus E, Oztekin N, et al. Vacuoliting megalencephalic leukoencephalopathy with subcortical cysts, mapped to chromosome 22qtel. Am J Hum Genet 2000;66:733–739.

    Article  PubMed  CAS  Google Scholar 

  299. Leegwater PA, Yuan BQ, van der Steen J, Mulders J, Konst AA, Boor PK, et al. Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts. Am J Hum Genet 2001;68:831–838.

    Article  PubMed  CAS  Google Scholar 

  300. Patrono C, Di Giacinto G, Eymard-Pierre E, Santorelli FM, Rodriguez D, De Stefano N, et al. Genetic heterogeneity of megalencephalic leukoencephalopathy and subcortical cysts. Neurology 2003;61:534–537.

    PubMed  CAS  Google Scholar 

  301. Blattner R, Von Moers A, Leegwater PA, Hanefeld FA, Van Der Knaap MS, Kohler W. Clinical and genetic heterogeneity in megalencephalic leukoencephalopathy with subcortical cysts (MLC). Neuropediatrics 2003;34: 215–218.

    Article  PubMed  CAS  Google Scholar 

  302. Singhal BS, Gorospe JR, Naidu S. Megalencephalic leukoencephalopathy with subcortical cysts. J Child Neurol 2003;18:646–652.

    Article  PubMed  Google Scholar 

  303. Gulati S, Kabra M, Gera S, Ghosh M, Menon PS, Kalra V.Infantileonset leukoencephalopathy with discrepant mild clinical course. Indian J Pediatr 2000;67:769–773.

    Article  PubMed  CAS  Google Scholar 

  304. Koeda T, Takeshita K. Slowly progressive cystic leukoencephalopathy with megalencephaly in a Japanese boy. Brain Dev 1998;20:245–249.

    Article  PubMed  CAS  Google Scholar 

  305. Brockmann K, Finsterbusch J, Terwey B, Frahm J, Hanefeld F.Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI. Neuroradiology 2003; 45:137–142.

    PubMed  CAS  Google Scholar 

  306. De Stefano N, Balestri P, Dotti MT, Grosso S, Mortilla M, Morgese G, Federico A. Severe metabolic abnormalities in the white matter of patients with vacuolating megalencephalic leukoencephalopathy with subcortical cysts. A proton MR spectroscopic imaging study. J Neurol 2001;248:403–409.

    Article  PubMed  Google Scholar 

  307. Brockmann K, Finsterbusch J, Terwey B, Frahm J, Hanefeld F. Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI. Neuroradiology 2003; 45:137–142.

    PubMed  CAS  Google Scholar 

  308. van der Knaap MS, Barth PG, Vrensen GF, Valk J. Histopathology of an infantile-onset spongiform leukoencephalopathy with a discrepantly mild clinical course. Acta Neuropathol (Berl) 1996;92:206–212.

    Article  Google Scholar 

  309. Babbitt DP, Tang T, Dobbs J, Berk R. Idiopathic familial cerebrovascular ferrocalcinosis (Fahr’s disease) and review of differential diagnosis of intracranial calcification in children. Am J Roentgenol 1969; 105:352–358.

    CAS  Google Scholar 

  310. Giroud M, Gouyon JB, Chaumet F, Cinquin AM, Chevalier-Nivelon A, Alison M, et al. A case of progressive familial encephalopathy in infancy with calcification of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Childs Nerv Syst 1986;2:47–48.

    Article  PubMed  CAS  Google Scholar 

  311. Mehta L, Trounce JQ, Moore JR, Young ID. Familial calcification of the basal ganglia with cerebrospinal fluid pleocytosis. J Med Genet 1986;23:157–160.

    Article  PubMed  CAS  Google Scholar 

  312. Tolmie JL, Shillito P, Hughes-Benzie R, Stephenson JBP. The Aicardi-Goutieres syndrome (familial, early onset encephalopathy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis). J Med Genet 1995;32:881–884.

    PubMed  CAS  Google Scholar 

  313. Kumar D, Rittey C, Cameron AH, Variend S. Recognizable inherited syndrome of progressive central nervous system degeneration and generalized intracranial calcification with overlapping phenotype of the syndrome of Aicardi and Goutieres. Am J Med Genet 1998;75:508–515.

    Article  PubMed  CAS  Google Scholar 

  314. Crow YJ, Jackson AP, Roberts E, van Beusekom E, Barth P, Corry P, et al. icardi-Goutieres syndrome displays genetic heterogeneity with one locus (AGS1) on chromosome 3p21. Am J Hum Genet 2000;67:213–221.

    Article  PubMed  CAS  Google Scholar 

  315. Bonnemann CG, Meinecke P. Encephalopathy of infancy with intracerebral calcification and chronic spinal fluid lymphocytosis—another case of the Aicardi-Goutieres syndrome. Neuropediatrics 1992;23:157–161.

    PubMed  CAS  Google Scholar 

  316. Lanzi G, Fazzi E, D’Arrigo S. Aicardi-Goutieres syndrome: a description of 21 new cases and a comparison with the literature. Eur J Paediatr Neurol 2002;6:A9–22.

    Article  PubMed  Google Scholar 

  317. McEntagart M, Kamel H, Lebon P, King MD. Aicardi-Goutieres syndrome: an expanding phenotype. Neuropediatrics 1998;29:163–167.

    Article  PubMed  CAS  Google Scholar 

  318. Lebon P, Badoual J, Ponsot G, Goutieres F, Hemeury-Cukier F, Aicardi J. Intrathecal synthesis of interferon-alpha in infants with progressive familial encephalopathy. J Neurol Sci 1988;84:201–208.

    Article  PubMed  CAS  Google Scholar 

  319. Blau N, Bonafe L, Krageloh-Mann I, Thony B, Kierat L, Hausler M, Ramaekers V. Cerebrospinal fluid pterins and folates in Aicardi-Goutieres syndrome: a new phenotype. Neurology 2003;61:642–647.

    PubMed  CAS  Google Scholar 

  320. Polizzi A, Pavone P, Parano E, Incorpora G, Ruggieri M. Lack of progression of brain atrophy in Aicardi-Goutieres syndrome. Pediatr Neurol 2001;24:300–302.

    Article  PubMed  CAS  Google Scholar 

  321. Kato M, Ishii R, Honma A, Ikeda H, Hayasaka K. Brainstem lesion in Aicardi-Goutieres syndrome. Pediatr Neurol 1998;19:145–147.

    Article  PubMed  CAS  Google Scholar 

  322. Barth PG.The neuropathology of Aicardi-Goutieres syndrome. Eur J Paediatr Neurol 2002;6:A27–31.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Child Neurology, Children’s National Medical Center, Washington, DC

    Adeline Vanderver MD

  2. Division of Genetics and Metabolism, Department of Pediatrics, Georgetown University, Washington, DC

    Andrea L. Gropman MD, FAAP, FACMG

  3. Division of Genetics and Metabolism, Department of Neurology, Georgetown University, Washington, DC

    Andrea L. Gropman MD, FAAP, FACMG

Authors
  1. Adeline Vanderver MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea L. Gropman MD, FAAP, FACMG
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Physiology and Pharmacology, City University of New York Medical School, New York, NY

    Patricia A. Broderick PhD

  2. Department of Neurology, New York University School of Medicine, New York, NY

    Patricia A. Broderick PhD  & Edwin H. Kolodny MD  & 

  3. NYU Comprehensive Epilepsy Center, New York, NY

    Patricia A. Broderick PhD

  4. Department of Chemistry and Physical Sciences, Pace University, Pleasantville, NY

    David N. Rahni PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Vanderver, A., Gropman, A.L. (2005). Childhood Mitochondrial Disorders and Other Inborn Errors of Metabolism Presenting With White Matter Disease. In: Broderick, P.A., Rahni, D.N., Kolodny, E.H. (eds) Bioimaging in Neurodegeneration. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-59259-888-5_22

Download citation

Publish with us

Policies and ethics

Search

Navigation