Summary
The leukodystrophies are degenerative diseases that involve primarily the white matter of the brain. The most common leukodystrophies result from known disturbances in the synthesis or catabolism of myelin such as a block in the catabolism of sulphatides and of galactocerebrosides, respectively, in metachromatic leukodystrophy and in Krabbe disease, or from synthesis of an abnormal proteolipid protein in Pelizaeus-Merzbacher disease. The cause of white matter involvement in other leukodystrophies remains unknown even though metabolic anomalies, such as accumulation of acetylaspartic acid in Canavan disease, have been demonstrated.
Common clinical features of the leukodystrophies include neurological deterioration following a period of normal development, predominant involvement of motor function at least initially, and absence of convulsions or myoclonus. Imaging — especially magnetic resonance — shows changes in density or signal from central white matter.
Most leukodystrophies feature suggestive symptoms and signs such as effects on peripheral nerves' myelin in Krabbe disease and metachromatic leukodystrophy, or X-linked inheritance and slow deterioration in Pelizaeus-Merzbacher disease.
Therapy of the leukodystrophies is purely symptomatic in most cases. Trials of bone marrow transplantation are being pursued for metachromatic leukodystrophy and adrenoleukodystrophy.
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References
Adams RD, Lyon G (1982)Neurology of Hereditary Metabolic Diseases of Children. New York: McGraw-Hill.
Aicardi J (1989) Progrediente Enzephalopathie-Syndrome unbekannter Ursache. In Hanefeld F, ed.Aktuelle Neuropädiatrie. Heidelberg: Springer Verlag, 3–15.
Aicardi J (1992)Diseases of the Nervous System in Childhood. London: MacKeith Press.
Aicardi J, Coutières F (1984) A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis.Ann Neurol 16: 60–65.
Aubourg PR, Sellier N, Chaussain JL, Kalifa G (1989) MRI detects cerebral involvement in neurologically asymptomatic patients with adrenoleukodystrophy.Neurology 39: 1619–1621.
Aubourg PR, Blanche S, Jambaqué I et al (1990) Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation.N Engl J Med 322: 1860–1866.
Bauman ML, Kemper TL (1982) Morphologic and histoanatomic observations of the brain in untreated phenylketonuria.Acta Neuropathol 58: 55–63.
Boespflug-Tanguy O, Cavagna A, Mimault C et al (1992) X-linked inherited demyelinating disease (Pelizaeus-Merzbacher disease); tight linkage with the proteolipoprotein gene (PLP) in 17 families.J Neurol 239 (Suppl.2): S7.
Borrett D, Becker LE (1985) Alexander disease; A disease of astrocytes.Brain 108: 367–385.
Burch M, Fensom AH, Jackson M, Pitts-Tucker T, Congdon PJ (1986) Multiple sulphatase deficiency presenting at birth.Clin Genet 30: 409–415.
Fiumara A, Pavone L, Siciliano L, Tine A, Parano E, Innico G (1990) Late-onset globoid cell leukodystrophy: report on seven more patients.Childs Nerv Syst 6: 194–197.
Gascon CG, Ozand PT, Mahdi H, Jamil A, Haider A, Brismar J (1990) Infantile CNS spongy degeneration in 14 cases: clinical update.Neurology 40: 1876–1882.
Gencic S, Abuelo O, Ambler M, Hudson LD (1989) Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein.Am J Hum Genet 45: 435–442.
Gieselman V (1991) An assay for the rapid detection of the arylsulfatase A pseudo-deficiency allele facilitates the diagnosis and the genetic counselling for metachromatic leukodystrophy.Hum Genet 86: 251–255.
Gieselman V, Polten A, Kreysing J, Kappler J, Fluharty A, Von Figura K (1991) Molecular genetics of metachromatic leukodystrophy.Dev Neurosci 13: 222–227.
Goebel HH, Harzer K, Ernst JP, Bohl J, Klein H (1990) Late-onset globoid cell leukodystrophy: unusual ultrastructural pathology and subtotal beta-galactocerebroside deficiency.J Child Neurol 5: 299–307.
Hagberg B (1984) Krabbe disease: clinical presentation of neurological variants.Neuropediatrics 15 (Suppl): 11–15.
Harbord MG, Harden P, Harding B, Brett EM, Baraitser M (1990) Megalencephaly and dysmyelination, spasticity, ataxia, seizures and distinctive neurophysiological findings in two siblings.Neuropediatrics 21: 164–168.
Kappler J, Watts RWE, Conzelmann E, Gibbs DA, Propping G, Gieselmann V (1991) Low arylsulfatase A activity and choreoathetotic syndrome in three siblings: differentiation of pseudodeficiency from metachromatic leukodystrophy.Eur J Pediatr 150: 287–290.
Kappler J, Von Figura K, Gieselman V (1992) Late-onset metachromatic leukodystrophy: molecular pathology in two siblings.Ann Neurol 31: 256–261.
Kendall BE (1993) Inborn errors and demyelination: MRI and the diagnosis of white matter disease.J Inher Metab Dis 16: 771–786.
Koeppen A, Ronca NA, Greenfield EH, Hans KB (1987) Defective biosynthesis of proteolipid protein in Pelizaeus-Merzbacher disease.Ann Neurol 21: 159–170.
Krivit W, Shapiro E, Kennedy W et al (1990) Treatment of late infantile metachromatic leukodystrophy by bone marrow transplantation.N Engl J Med 322: 28–32.
Kolodny EH, Raghavan S, Krivit W (1991) Late-onset Krabbe disease (globoid-cell leukodystrophy): clinical and biochemical features of 16 cases.Dev Neurosci 13: 232–239.
Lyon G, Hagberg B, Evrard P, Allaire C, Pavone L, Vanier M (1991) Symptomatology of late onset Krabbe leukodystrophy: the European experience.Dev Neurosci 13: 240–244.
MacFaul R, Cavanagh N, Lake BD, Stephens R, Whitfield AE (1982) Metachromatic leukodystrophy: review of 38 cases.Arch Dis Child 57: 168–175.
Meyding-Lamade UK, Pietz J, Fahrendorf G, Sartor KJ (1992) Early treated phenylketonuria: do MR images parallel clinical, biochemical and neurophysiological data?J Neurol 239 (Suppl 2): S5.
Moser HW (1989) Peroxisomal disease.Adv Pediatr 36: 1–38.
Moser HW, Moser AB, Naidu S, Bergin A (1991) Clinical aspects of adrenoleukodystrophy and adrenomyeloneuropathy.Dev Neurosci 13: 254–261.
Pearsen KD, Gean-Marton AD, Levy HL, Davis K (1990) Phenylketonuria: MR imaging of the brain with clinical correlation.Radiology 177: 437–440.
Phelps M, Aicardi J, Vanier M (1991) Late-onset Krabbe leukodystrophy. A report of four cases.J Neurol Neurosurg Psychiatr 54: 293–296.
Polten A, Fluharty AL, Kappler J, Von Figura K, Gieselman V (1991) Molecular basis of different forms of metachromatic leukodystrophy.N Engl J Med 324: 18–22.
Pratt VM, Troffater JA, Schinzel A, Dlonhy SR, Conneally PM, Hodes ME (1991) A new mutation in the proteolipid protein (PL) gene in a German family with Pelizaeus-Merzbacher disease.Am J Med Genet 38: 136–139.
Rapin I (1991) Autistic children: diagnostic and clinical features.Pediatrics 87: 751–760.
Rizzo WB, Philipps MW, Dammann AL et al (1987) Adrenoleukodystrophy: dietary oleic acid lowers hexacosanoate levels.Ann Neurol 21: 232–239.
Sasaki M, Sakuragawa N, Takashima S, Hanaoka S, Arima M (1991) MRI and CT findings in Krabbe disease.Pediatr Neurol 7: 283–288.
Taylor MJ, Fagan ER (1990) Somatosensory evoked potentials: a review of their application in paediatric neurology. In Galai V, ed.Maturation of the CNS and Evoked Potentials. Amsterdam: Elsevier, 119–124.
Uziel G, Bertini E, Bardelli P, Rimoldi M, Gambetti M (1991) Experience on therapy of adrenoleukodystrophy and adrenomyeloneuropathy.Dev Neurosci 13: 274–279.
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Aicardi, J. The inherited leukodystrophies: A clinical overview. J Inherit Metab Dis 16, 733–743 (1993). https://doi.org/10.1007/BF00711905
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DOI: https://doi.org/10.1007/BF00711905