Biochemical Studies in Sphingomyelin Storage Disorders

  • Marie T. Vanier
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 101)


Inherited sphingomyelin storage disorders, more often referred to as Niemann-Pick disease, constitute a heterogeneous group both from a clinical and a biochemical point of view. The division into four types, first proposed by Crocker in 1961 (5), which is still widely used, delineates an infantile neuropathic form, or type A, a non-neuropathic form or type B, a subacute or juvenile form, also called type C, and a so-called Nova Scotia variant or type D. From a clinical point of view, the classification appears quite satisfactory as regards type A and B. Biochemically, a severe storage of sphingomyelin in visceral organs and a profound deficiency of sphingomyelinase have constantly been found in patients with these two phenotypes, but storage in brain only occurs in type A. With regard to the other forms of the disease, there is however much confusion. Delineation between type C and D is quite unclear. Furthermore, on the basis of specific clinical signs, other subgroups have been proposed (14), and some patients reported in the literature have been considered to represent a new nosological entity (26). With regard to the biochemical findings in those patients, a varying degree of sphingomyelin storage and either partial deficiency or normal activity of sphingomyelinase have been reported, without systematic correlation to a given clinical form.


Skin Fibroblast Total Phospholipid Lysosomal Storage Disease Sodium Taurocholate Cultivate Skin Fibroblast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    BARATON, G. REVOL, A.- Activateur des sphingohydrolases et nature du déficit en sphingomyelinase dans la maladie de Niemann-Pick type A, B et C. Clin.Chim. Acta, 76: 339–343, 1977.Google Scholar
  2. 2.
    BRADY, R.O., KANFER, J.N., MOCK, M.B. FREDRICKSON, D.S.The metabolism of sphingomyelin.II. Evidence of an enzymatic deficiency in Niemann-Pick disease. Proc.Nat.Acad.Sci. USA, 55: 366–369, 1966.CrossRefGoogle Scholar
  3. 3.
    CALLAHAN, J.W., KHALIL, M. PHILIPPART, M.- Sphingomyelinases in human tissues. II. Absence of a specific enzyme from liver and brain of Niemann-Pick disease, type C. Pediat. Res., 9: 908–913, 1975.Google Scholar
  4. 4.
    CRAWFORD, N.- An improved method for the determination of free and total cholesterol using the ferric chloride reaction. Clin.Chim.Acta, 4: 357–367, 1958.CrossRefGoogle Scholar
  5. 5.
    CROCKER, A.C.- The cerebral defect in Tay-Sachs disease and Niemann-Pick disease. J. Neurochem., 7: 69–80, 1961.CrossRefGoogle Scholar
  6. 6.
    CROCKER, A.C. FARBER, S.- Niemann-Pick disease. A review of eighteen patients. Medicine, 37: 1–98, 1958.PubMedCrossRefGoogle Scholar
  7. 7.
    FREDRICKSON, D.S. SLOAN, H.R.- Sphingomyelin lipidoses: Niemann-Pick disease. In The Metabolic Basis of Inherited Disease, J.B.Stanbury, J.B.Wyngaarden D.S.Fredrickson (eds.), Mc Graw Hill Inc., New York, 1972, pp 783–807.Google Scholar
  8. 8.
    HARTREE, E.F.- Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal. Biochem., 48: 122–127, 1972.Google Scholar
  9. 9.
    IVEMARK, B.I., SVENNERHOLM, L., THOREN, C. TUNELL, R.Niemann-Pick disease in infancy. Report of two siblings with clinical, histological and chemical studies. Acta Paediat. Scand., 52: 391–404, 1963.Google Scholar
  10. 10.
    KAMOSHITA, S., ARON, A.M., SUZUKI, K., SUZUKI, K.- Infantile Niemann-Pick disease. A chemical study with isolation and characterization of membranous cytoplasmic bodies and myelin. Amer.J.Dis. Child., 117: 379–374, 1969.Google Scholar
  11. 11.
    KARPATI, G., CARPENTER, S., Wolfe, L.S. Andermann, F.- Juvenile dystonic lipidosis. An unusual form of neurovisceral storage disease. Neurology, 27: 32-42, 1977.Google Scholar
  12. 12.
    de LEON, G.A., KABACK, M.M., ELFENBEIN, I.B., PERCY, A.K., BRADY, R.O.- Juvenile dystonic lipidosis. Hopkins Med. J., 125: 62–77, 1969.Google Scholar
  13. 13.
    Long, R.G., Lake, B.D., Pettit, J.E., Scheuer, P.J. SHERLOCK, S.-Adult Niemann-Pick disease. Its relationship to the syndrome of the sea-blue histiocyte. Amer.J. Med., 62: 627–635, 1977.CrossRefGoogle Scholar
  14. 14.
    NEVILLE, B.G.R., LAKE, B.D., STEPHENS, R. SANDERS, M.D.A neurovisceral storage disease with vertical supranuclear ophtalmoplegia, and its relationship to Niemann-Pick disease. A report of nine patients. Brain, 96: 97–120, 1973.PubMedCrossRefGoogle Scholar
  15. 15.
    NORMAN, R.M., FORRESTER, R.M. TINGEY, A.H.- The juvenile form of Niemann-Pick disease. Arch.Dis. Childh., 42: 91–96, 1967.CrossRefGoogle Scholar
  16. 16.
    PHILIPPART, M., GAUTIER, M., GATTI, R., DURAND, P. VAMOSHURWITZ, E.- Sphingomyelin metabolism in the Niemann-Pick syndrome. Proc.Int.Soc. Neurochem., 6: 417, 1977.Google Scholar
  17. 17.
    PHILIPPART, M., MARTIN, L., MARTIN, J.J. MENKES, J.H.- NiemannPick disease. Morphologic and biochemical studies in the visceral form with late central nervous system involvement (Crocker“s group C). Arch. Neurol., 20: 227–238, 1969.Google Scholar
  18. 18.
    ROUSER, G., Kritchevsky, G., Yamamoto, A., Knudson, A.G. Simon, G.- Accumulation of a glycerolphospholipid in classical Niemann-Pick disease. Lipids, 3: 287–290, 1968.PubMedCrossRefGoogle Scholar
  19. 19.
    SAKURAGAWA, N., SAKURAGAWA, M., KUWABARA, T., PENTCHEV, P.G., BARRANGER, J.A. Brady, R.O.- Niemann-Pick disease experimental model. Sphingomyelinase reduction induced by AY 9944. Science, 196: 317–319, 1977.PubMedCrossRefGoogle Scholar
  20. 20.
    SCHNEIDER P.D. KENNEDY, E.P.- Sphingomyelinase in normal human spleens and in spleens from subjects with Niemann-Pick disease. J.Lipid Res., 8: 202–209, 1967.Google Scholar
  21. 21.
    STOFFEL, W., LEKIM, D. TSCHUNG, T.S.- A simple chemical method for labelling phosphatidylcholine and sphingomyelin in the choline moiety. Z.physiol. Chem., 352: 1058–1064, 1971.Google Scholar
  22. 22.
    SVENNERHOLM, L.- Distribution and fatty acid composition of phosphoglycerides in normal human brain. J. Lipid Res., 9: 570–579, 1968.Google Scholar
  23. 23.
    SVENNERHOLM, L., HAKANSSON. G. VANIER, M.T.- Chemical pathology of Krabbe disease. IV. Studies of galactosylceramide and lactosylceramide ß-galactosidases in brain, white blood cells and amniotic fluid cells. Acta Paediat. Scand., 64: 649–656, 1975.Google Scholar
  24. 24.
    SVENNERHOLM, L. VANIER, M.T.- The distribution of lipids in the human nervous system.II. Lipid composition of human foetal and infant brain. Brain Res., 49: 458–468, 1972.Google Scholar
  25. 25.
    VAN HOOF, F. HERS, H.G.- The abnormalities of lysosomal enzymes in mucopolysaccharidoses. European J. Biochem., 7: 34–44, 1968.Google Scholar
  26. 26.
    WIEDEMANN, H.R., DEBUCH, H., LENNERT, H., CAESAR, R., BLUMCKE, S., KARMS, D., TOLKSDORF, M., SENG, P.N., KORENKE, H.D., GERKEN, H., FREITAG, F. DÖRNER, Kl.- Uber eine infantile-juvenile, subchronisch Verlaufende, den Sphingomyelinosen (Niemann-Pick) anzureihende Form der Lipidosen-ein neuer Typ ? Z. Kinderheilk., 112: 187–225, 1972.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • Marie T. Vanier
    • 1
  1. 1.Fondation GilletHôpital Sainte-EugénieSaint Genis LavalFrance

Personalised recommendations