Summary
A clinical, neuropathological and neurochemical study of a case of Anderson-Fabry's disease is described.
The clinical course mainly consisted of repeated icuts with major involvement of the CNS.
The neuropathological examination is dominated by severe alterations in the cerebral vessels due to glycolipid deposits on the walls, with reduction or occlusion of the lumen. This is correlated with secondary ischaemic foci scattered throughout the cortex as well as through the white matter. In addition, the cells of the cerebral cortex, thalamus, basal ganglia, amygdala, cerebellar and olivary nuclei show a marked accumulation of lipofuscin.
Biochemical examination reveals a threefold increase in galactolipids due to the specific α-galactosidase deficiency. Cholesterol is reduced secondarily to ischaemic myelin damage. Glycosaminoglycans uronic acid is increased in cytosol and membrane-bound fractions which could be related to reactive gliosis. Glycoprotein sugars show a decrease in N-acetyl-neuraminic acid and fucose as well as an increase in hexosamines and hexoses in membrane-bound fraction, while in cytosol fraction all sugars are increased.
This suggests that the α-galactosidase deficiency can alter not only the glycolipid but also the glycoprotein metabolism, resulting in a higher presence of hexosamines and hexoses-rich glycoproteins.
Similar content being viewed by others
References
Allen N (1961) β-Glucuronidase activities in tumours of the nervous system. Neurology (Minneap) 11:578–596
Allen N, Clendenon NR, Koestner A, Abe H (1970) The use of nitrosamine induced nervous system tumors of rat for biochemical investigations. Trans Am Neurol Assoc 95:140–142
Bitter T, Muir HM (1962) A modified uronic acid carbazole reaction. Anal Biochem 4:330–334
Boas NF (1953) Method for the determination of hexosamines in tissue. J Biol Chem 204:553–563
Brunngraber EG (1972) Neuropathology of glycopeptides derived from brain glycoproteins. In: Zambotti V, Tettamanti G, Annigoni MG (eds) Glycolipid, glycoproteins and mucopolysac-charides of the nervous system. Plenum Press, New York (Adv Exp Med Biol 25:255–271)
Brunngraber EG, Brown BD, Aro A (1974) Glycoproteins in brain tissue of the O-variant of GM 2 gangliosidosis. J Neurochem 22:125–128
Brunngraber EG, Brown BD, Hof H (1971) Determination of gangliosides, glycorproteins and glycosaminoglycans in brain tissue. Clin Chem Acta 32:159–170
Caulet T, Germain P, Adnet JJ, Hopfner C, Pluot M (1967) Deux cas familiaux de maladie de Fabry. Etude structurale et ultrastructurale. Ann Anat Pathol (Paris) 12:49–70
Christensen Lou HO (1966) A biochemical investigation of angiokeratoma corporis diffusum. Acta Pathol Microbiol Scand 68:332–342
Christensen Lou HO, Reske-Nielsen E (1971) The central nervous system in Fabry's disease. A clinical, pathological and biochemical investigation. Arch Neurol 25:351–359
De Gasperi R, Rapelli S, Lindi C, Berra B (1981) Studies on glycoprotein metabolism in different types of sphingolipidosis. J Inher Met Dis 4:159–160
Di Benedetta C, Brunngraber EG (1975) Separation of glycopeptides derived from brain glycoproteins by gel filtration. Ital J Biochem 24:97–101
Di Benedetta C, Chang I, Brunngraber EG (1971) Electrophoretic separation and properties of soluble glycoproteins extracted from whole rat brain tissue. Ital J Biochem 20:49–65
Dische Z, Shettles LB, Osnos M (1949) New specific color reaction of hexoses and spectrophotometric micromethods for their determination. Arch Biochem 22:169–184
Federico A (1980) Glycoconjugate changes in several metabolic diseases of the central nervous system. In: Lajtha AL (ed) Progress in clinical and biological research. Liss, New York (Neurochemistry and Clinical Neurology 39:465)
Federico A, Guazzi GC, Di Benedetta C (1977) Glycosaminoglycans and glycoproteins in metachromatic leucodystrophy. Eur Neurol 15:163–168
Federico A, Robert J, Zanetta JP, Guazzi GC (1981a) Sanfilippo A syndrome (MPSose III A): A neurochemical study. Ital J Neurol Sci 2:119–127
Federico A, Robert J, Zanetta JP, Guazzi GC (1981b) Cherry-red spot and myoclonus syndrome: Neurochemical study of a case. Perspect Inher Met Dis 4:281–299
Gemignani F, Pietrini V, Tagliavini F, Lechi A, Neri TM, Asinari A, Savi M (1979) Fabry's disease with familial lymphedema of the lower limbs. Eur Neurol 18:84–90
Gonatas NK, Terry RD, Winkler R, Korey SR, Gomez CJ, Stein A (1963) Case of juvenile lipidosis: The significance of electron microscopic and biochemical observations of a cerebral biopsy. J Neuropathol Exp Neurol 22:557–580
Grunnet ML, Spilsbury PR (1973) The central nervous system in Fabry's disease. An ultrastructural study. Arch Neurol 28:231–234
Haberland C, Brunngraber EG, Withing L, Daniels A (1973) Juvenile metachromatic leucodistrophy. Case report with clinical, histopathological, ultrastructural and biochemical observations. Acta Neuropathol (Berl) 26:93–106
Idler LR, Baumann AC (1953) Skin sterols: III-sterol structure and the Liebermann-Burchard reaction. J Biol Chem 203:389–396
Jensen E (1966) On the pathology of angiokeratoma corporis diffusum (Fabry). Acta Pathol Microbiol Scand 68:313–331
Kahn P (1973) Anderson-Fabry disease: A histopathological study of three cases with observations on the mechanism of production of pain. J Neurol Neurosurg Psych 36:1053–1062
Kint JA (1970) Fabry's disease: Alpha-galactosidase deficiency. Science 167:1268–1269
Lowden JA, Callahan JW, Gravel RA, Skomorowski MA, Becker L, Groves J (1981) Type 2 GMI gangliosidosis with logn survival and neuronal ceroid lipofuscinosis. Neurology (Minneap) 31:719–724
Miyatake T, Ariga T (1972) Sphingoglycolipids in the nervous system in Fabry's disease. J Neurochem 19:1911–1916
Oldfors A, Sourander P (1981) Storage of lipofuscin in neurons in mucopolysaccharidosis. Report on a case of Sanfilippo's syndrome with histochemical and electronmicroscopic findings. Acta Neuropathol (Berl) 54:287–292
Rahman AN, Lindenberg R (1963) The neuropathology of hereditary dystropic lipidosis. Arch Neurol 9:373–385
Robert J, Rebel G (1975) Quantification of neutral glycolipids by thin-layer chromatography on precoated plates. J Chrom 110:393–397
Roels H, Quatacker J, Kint A, Vander Eecken H, Vrints L (1970) Generalized gangliosidosis-GMI: Landing disease II. Morphological study. Eur Neurol 3:129–160
Schatzki PF, Kipreos B, Payne J (1979) Fabry's disease. Primary diagnosis by electron microscopy. Am J Surg Pathol 3:211–219
Schibanoff JM, Kamoshita S, O'Brien JS (1969) Tissue distribution of glycosphingolipids in a case of Fabry's disease. J Lipid Res 10:515–520
Scriba K (1951) Zur Pathogenese des Angiokeratoma corporis diffusum Fabry mit cardio-vaso-renalem Symptomenkomplex. Verh Dtsch Ges Pathol 34:221–226
Steward VW, Hitchcock C (1968) Fabry's disease (Angiocheratoma corporis diffusum). A report of 5 cases with pain in the extremities as the chief symptom. Pathol Eur 3:377–388
Suzuki K (1964) A sample and accurate micromethod for quantitative determination of ganglioside pattern. Life Sci 3:1227–1233
Suzuki K, Suzuki K, Chen G (1968) Morphological, histochemical and biochemical studies on a case of systemic late infantile lipidosis (generalized gangliosidosis). J Neuropathol Exp Neurol 27:15–38
Svennerholm L (1957) Quantitative estimation of gangliosides in senile human brains. Acta Soc Med Upsal 62:1–16
Tabira T, Goto I, Kuroiwa Y (1974) Neuropathological and biochemical studies in Fabry's disease. Acta Neuropathol (Berl) 30:345–354
Warren L (1959) The thiobarbituric acid assay of sialic acid. J Biol Chem 234:1971–1974
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tagliavini, F., Pietrini, V., Gemignani, F. et al. Anderson-Fabry's disease: Neuropathological and neurochemical investigation. Acta Neuropathol 56, 93–98 (1982). https://doi.org/10.1007/BF00690579
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00690579