Summary
Biochemical analyses were performed on cerebral biopsies from three siblings with metachromatic leukodystrophy, and from autopsy tissue obtained 6 months later. The lipids of all gray matter samples were relatively normal, with the exception of an elevated sulfatide: cerebroside ratio. The white matter samples were grossly abnormal and showed a progression in severity of biochemical abnormalities with duration of the discase. Sulfatides were 4–8-fold higher than normal and the ratio of cerebrosides to sulfatides ranged from 0.13 to 0.26, compared to the nommal value of about 4.0.
Myelin was isolated in very low yield, but had normal morphology. As others have reported, it had the same chemical defect as whole white matter: sulfatides were 7–8 times higher than normal and cerebrosides were reduced by more than half. The fatty acid compositions of the myelin sphingolipids were found to be of much longer average chain length than those in affected white matter. In myelin, the unsubstituted fatty acids of cerebrosides and sphingomyclin had a higher percentage of short chains than found in normal myelin, but were less abnormal than those in whole white matter, whereas the unsubstituted and α-nydroxy acids of sulfatides and the α-hydroxy acids of cerebrosides were not deficient in long chains. These data indicate that there are at least two compartments of sphingolipids in MLD white matter, each having different average chain lengths.
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References
Abramson MB, Norton WT, Katzman R (1965) Study of ionic structures in phospholipids by infrared spectra. J Biol Chem 240:2389–2395
Austin J (1959) Metachromatic sulfatides in cerebral white matter and kidney. Proc Soc Exp Biol Med 100:361–364
Autilio LA, Norton WT, Terry RD (1964) The preparation and some properties of purified myelin from the central nervous system. J Neurochem 11:17–27
Cumings JN (1969) The lipid composition of pure myelin in some demyelinating disorders. J Neuropathol Pol 7:255–265
Dulaney JT, Moser HW (1978) Sulfatide lipidosis: Metachromatic leukodystrophy. In: Stanbury JB, Wyngaarden JB, Frederickson DS (eds) The metabolic basis of inherited disease, 4th edn. McGraw-Hill, New York, pp 770–809
Folch J, Lees MS, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509
Jatzkewitz H (1958) Zwer Typen von Cerebrosid-Schwefel-Säureestern als sog. “Paralipioide” und Speichersubstanzen bei der Leukodystrophie. Type Scholz (Metachromatische Form der diffusen Sklerose). Z Physiol Chem 311:279–282
Malone MJ, Stoffyn P (1966) A comparative study of brain and kidney glycolipids in metachromatic leucodystrophy. J Neurochem 13:1037–1045
Malone MJ, Sakuragawa N, Szoke M (1975) A comparative study of myelin fractions from metachromatic and globoid leucodystrophies. Neurology 9:827–832
Metcalfe LD, Schmitz AA (1961) The rapid preparation of fatty acid esters for gas chromatographic analysis. Anal Chem 33:363–364
Morell P, Bornstein MB, Raine CS (1976) Diseases involving myelin. In: Albers RW, Siegel GJ, Katzman R, Agranoff BW (eds) Basic neurochemistry, 2nd edn. Little, Brown, Boston, pp 581–604
Norton WT (1977) Chemical pathology of diseases involving myelin. In: Morell P (ed) Myelin. Plenum Press, New York, pp 383–413
Norton WT, Autilio LA (1965) The chemical composition of bovine CNS myelin. Ann NY Acad Sci 122:77–85
Norton WT, Autilio LA (1966) The lipid composition of purified bovine brain myelin. J Neurochem 13:213–222
Norton WT, Poduslo SE (1966) Metachromatic leukodystrophy: Chemically abnormal myelin and cerebral biopsy studies of three siblings. In: Ansell GB (ed) Variation in the chemical composition of the nervous system. Pergamon Press, Oxford, p 82
Norton WT, Poduslo SE (1973) Myelination in rat brain: Method of myelin isolation. J Neurochem 21:749–757
Norton WT, Poduslo SE, Suzuki K (1966) Subacute sclerosing leukoencephalitis. II. Chemical studies including abnormal myelin and an abnormal ganglioside pattern. J Neuropathol Exp Neurol 25:582–597
O'Brien JS, Sampson LE (1966) Myelin membrane: A molecular abnormality. Science 150:1613–1614
Poduslo SE, Miller K, Jang Y (1982) Biochemical studies of the late infantile form of metachromatic leukodystrophy. Acta Neuropathol (Berl) 57:13–22
Schaumburg HH, Raine CS (1977) The neurology of myelin diseases. In: Morell P (ed) Myelin: Plenum Press, New York, pp 325–351
Ställberg-Stenhagen S, Svennerholm L (1965) Fatty acid composition of human brain sphingomyelin: Normal variation with age and changes during myelin disorders. J Lipid Res 6:46–55
Suzuki K (1967) Ganglioside patterns of normal and pathological brains. In: Aronson SM, Volk BW (eds) Inborn disorders of sphingolipid metabolism. Pergamon Press, New York, pp 215–230
Suzuki K (1978) Biochemistry of myelin disorders. In: Waxman SG (ed) Physiology and pathobiology of axons. Raven Press, New York, pp 337–347
Suzuki K, Suzuki K, Chen GC (1967) Isolation and chemical characterization of metachromatic granules from a brain with metachromatic leukodystrophy. J Neuropathol Exp Neurol 26:537–550
Taketomi T, Kawamura N (1968) Cerebroside and sulfatide isolated from the cerebral frontal lobe of a patient with metachromatic leucodystrophy. Med J Shinshu Univ 13:103–108
Terry RD (1970) Electron microscopy of selected neurolipidoses. In: Handbook of clinical neurology, vol. 10. Leucodystrophies and poliodystrophies. North-Holland, Amsterdam, pp 362–384
Yabuuchi H, Okada S, Honda M, Hanai J (1968) Pathological and biochemical study of metachromatic leucodystrophy. Med J Osaka Univ 18:361–371
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Supported by U.S.P.H.S. grants NS-02476 and NS-03356
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Norton, W.T., Poduslo, S.E. Biochemical studies of metachromatic leukodystrophy in three siblings. Acta Neuropathol 57, 188–196 (1982). https://doi.org/10.1007/BF00685388
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DOI: https://doi.org/10.1007/BF00685388