Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Tangier disease. A case with sensorimotor distal polyneuropathy and lipid accumulation in striated muscle and vasa nervorum

  • 72 Accesses

  • 16 Citations


A 65-year-old man with Tangier disease (analphalipoproteinemia) had had a progressive sensorimotor distal neuropathy with sensory ataxia for 1 year. Muscle biopsy demonstrated excess lipid vacuoles on histochemical and electron-microscopic techniques. Sural nerve biopsy showed a marked loss of large fibers and an increase in small myelinated fibers, with presence of remyelinating fibers and clusters of regeneration; a few aspects of active demyelination and some onion-like formations were also present. Lipid accumulation chiefly affected the Schwann cells of unmyelinated fibers and, to a lesser degree, of myelinated fibers, endoneurial fibroblast, and vasa nervorum. Teased fibers showed prevalent aspects of de-/remyelination and, often in association, marked myelin wrinkling suggesting axonal atrophy.

This Tangier patient differs from known cases for the presence of a distal symmetrical sensorimotor polyneuropathy (not previously reported in Tangier disease) and because of the morphological findings of de-/remyelination coexisting with aspects of axonal atrophy and previous degeneration, and of lipid accumulation within striated muscle and vasa nervorum. This latter finding contrasts with the assumption that in Tangier disease vessel walls are not a site of lipid storage: probably the vasa nervorum are different, in this respect, from other vessels, because of the intense lipid metabolism of the nervous tissue. Thus we suggest that involvement of vasa nervorum in Tangier disease may be more important than previously suspected, possibly playing a role in the causation of neuropathy.

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


  1. Assmann G, Schaefer H-E (1978) High density lipoprotein deficiency and lipid deposition in Tangier disease. In: Carlson LA et al (eds) International Conference on Atherosclerosis. Raven Press, New York, pp 97–101

  2. Bale PM, Clifton-Bligh P, Benjamin BNP, Whyte HM (1971) Pathology of Tangier disease. J Clin Pathol 24:609–616

  3. Brook JG, Lees RS, Yules JH, Cusack B (1977) Tangier disease (α-lipoprotein deficiency). JAMA 238:332–334

  4. Dyck PJ, Ellefson RD, Yao JK, Herbert PN (1978) Adultonset of Tangier disease. 1. Morphometric and pathological studies suggesting delayed degradation of neutral lipids after fiber degeneration. J Neuropathol Exp Neurol 37:119–137

  5. Dyck PJ, Johnson WJ, Lambert EH, O'Brien PC (1971) Segmental demyelination secondary to axonal degeneration in uremic neuropathy. Mayo Clin Proc 46:400–431

  6. Engel WK, Dorman JD, Levy RI, Fredrickson DS (1967) Neuropathy in Tangier disease: alpha-lipoprotein deficiency manifesting as familial recurrent neuropathy and intestinal lipid storage. Arch Neurol 17:1–9

  7. Farinon AM, Marbini A, Gemignani F, Govoni E, Bragaglia MM, Sianesi M, Tedeschi F (1984) Significance and clinical correlations of striated muscle and peripheral nerve changes caused by chronic arterial insufficiency: histological, histochemical and ultrastructural study. Clin Neuropathol 6:240–252

  8. Ferrans VJ, Fredrickson DS (1975) The pathology of Tangier disease. A light- and electron-microscopic study. Am J Pathol 78:101–136

  9. Fredrickson DS, Gotto AM, Levy RI (1972) Familial lipoprotein deficiency (abetalipoproteinemia, hypobetalipoproteinemia, and Tangier disease). In: Stanbury JB, Wyngarden JB, Fredrickson DS (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 493–530

  10. Gemignani F, Marbini A, Bragaglia MM, Govoni E (1984) Pathological study of the sural nerve in Fabry's disease. Eur Neurol 23:173–181

  11. Goebel HH, Pilz H, Argyrakis A (1977) Adult metachromatic leukodystrophy. II. Ultrastructural findings in peripheral nerve and skeletal muscle. Eur Neurol 15:308–317

  12. Hager H, Zimmermann P (1979) Licht- und elektronenmikroskopische sowie cytochemische Untersuchungen an peripheren Nerven beim Morbus Tangier. Acta Neuropathol (Berl) 45:53–59

  13. Haas LF, Bergin JD (1970) Alpha-lipoprotein deficiency with neurologic features. Aust Ann Med 1:76

  14. Hoffman HN, Fredrickson DS (1965) Tangier disease (familial HDL deficiency): Clinical and genetic features in two adults. Am J Med 39:582–593

  15. Kocen RS, Lloyd JK, Lascelles PT, Fosbrooke AS, Williams D (1967) Familial alpha-lipoprotein deficiency (Tangier disease) with neurologic abnormalities. Lancet I:1341–1345

  16. Marbini A, Gemignani F, Manganelli P, Govoni E, Bragaglia MM, Ambanelli U (1982) Hypertrophic neuropathy in Sjogren's syndrome. Acta Neuropathol (Berl) 57:309–312

  17. Pollock M, Nukada H, Frith RW, Simcock JP, Allpress S (1983) Peripheral neuropathy in Tangier disease. Brain 106:911–928

  18. Schaefer EJ, Kay LL, Zech LA, Brewer HB (1982) Tangier disease. High density lipoprotein deficiency due to defective metabolism of an abnormal apolipoprotein A-I (apo A-I Tangier). J Clin Invest 70:934–945

  19. Schaefer EJ, Zech LA, Schwarte DE, Brewer HB (1980) Coronary heart disease prevalence and other clinical features in familial high-density lipoprotein deficiency (Tangier disease). Ann Intern Med 93:261–266

  20. Sima AAF, Robertson DM (1978) Involvement of peripheral nerve and muscle in Fabry's disease. Arch Neurol 35:291–301

  21. Sutherland WHF, Pollock M (1984) Endoneurial ATPase activity in Tangier disease and other peripheral neuropathies. Muscle Nerve 7:447–453

  22. Thomas PK, Hollinrake K, Lascelles RG, O'Sullivan DJ, Baillod RA, Moorhead JF, Mackenzie JC (1971) The polyneuropathy of chronic renal failure. Brain 94:761–780

  23. Vergani CG, Plancher AC, Zuin M, Cattaneo M, Tramaloni C, Maccari S, Roma P, Catapano AL (1984) Bile lipid composition and haemostatic variables in a case of high density lipoprotein deficiency (Tangier disease). Eur J Clin Invest 14:49–54

Download references

Author information

Correspondence to A. Marbini.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Marbini, A., Gemignani, F., Ferrarini, G. et al. Tangier disease. A case with sensorimotor distal polyneuropathy and lipid accumulation in striated muscle and vasa nervorum. Acta Neuropathol 67, 121–127 (1985). https://doi.org/10.1007/BF00688132

Download citation

Key words

  • Tangier disease
  • Peripheral neuropathy
  • Lipid storage
  • Sural nerve