Summary
Fabry's disease was diagnosed in an adult patient as a lipid storage-induced non-obstructive hypertrophic cardiomyopathy. Stable angina pectoris started 15 years before death, was followed by slowly progressive heart failure and repeated pulmonary thromboembolism with death at 63 years. Autopsy disclosed enormous cardiomegaly (1100 g), cardiac storage of ceramide trihexoside (CTH) of the same intensity as in classical cases of generalized Fabry's disease (11 mg lipid/g wet weight) restricted to cardiocytes. Other tissues (liver, kidney, brain, pancreas, pulmonary artery, coronary arteries) were free of storage. Using proton magnetic resonance analysis on formaldehyde-fixed tissue the stored CTH was identified as globotriaosylceramide. It was enzymatically degradable by control cell cultures but left uncleaved by mutant reference Fabry cells. Alpha — galactosidase activities in peripheral leucocytes of all four of the patient's daughters were in the heterozygous range. The diagnostic difficulties in this monosymptomatic novel variant of Fabry's disease are stressed.
Similar content being viewed by others
References
Abe T, Ogawa K, Fujiwara Y, Sugamata K, Nagashima K (1988) Specific accumulation of Gb Cer in cardiac tissues in novel cases of Fabry's disease. Proceedings of the Third International Conference on the Biomedical Significance of Glycolipids, September 1988, Tokyo
Bannwart F (1982) Licht- und elektronenmikroskopischer Herzbefund 12 Jahre nach erfolgreicher Nierentransplantation. Schweiz Med Wochenschr 112:1742–1747
Becker AE, Schoorl R, Balk AG, Heide RM van der (1975) Cardiac manifestation of Fabry's disease. Report of a case with mitral insufficiency and electrocardiographic evidence of myocardial infarction. Am J Cardiol 36:829–835
Cohen IS, Fluri-Lundeen J, Wharton TP (1983) Two dimensional echocardiographic similarity of Fabry's disease to cardiac amyloidosis: a function of ultrastructural analogy? J Clin Ultrasound 11:437–441
Colucci WS, Lorell BH, Schoen FJ, Warhol MJ, Grossman W (1982) Hypertrophic obstructive cardiomyopathy due to Fabry's disease. N Engl J Med 307:926–928
Dabrowski J, Hanfland P, Egge H (1980) Structural analysis of glycosphingolipids by high resolution H nuclear magnetic resonance. Biochemistry 19:5652–5658
Dean KJ, Sweeley CC (1977) Fabry disease. In: Glew RH, Peters SP (eds) Practical enzymology of sphingolipidoses. Liss, New York, pp 173–216
Desnick RJ, Bishop DF (1989) Fabry Disease: alpha-galactosidase deficiency; Schindler disease: alpha-N-acetylgalactosaminidase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 1751–1796
Desnick RJ, Blieden LC, Sharp HL, Hofschire PJ, Moller JH (1976) Cardiac valvular anomalies in Fabry disease. Clinical, morphologic, and biochemical studies. Circulation 54:818–825
Elleder M (1977) Lipid histochemistry — a critical survey. Acta Histochem (Jena) [Suppl] 19:239–265
Elleder M, šmíd F (1977) Lysosomal non-lipid component of Gaucher's cells. Virchows Arch [B] 26:133–138
Esselman WJ, Laine RA, Sweeley CC (1972) Isolation and characterization of glycosphingolipids. In: Ginsburg V (ed) Methods in enzymology, vol XXVIII. Complex carbohydrates, part B. Academic Press, New York, pp 141–156
Frenzel H, Kuhn H, Hort W (1983) Die diagnostische Bedeutung der Endomyokardialbiopsie (EMcB) bei hypertrophischer nicht obstruktiver Kardiomyopathie (CMP) (abstract): Z Kardiol 72 [Suppl 1]:8
Fritz P, Schneider H, Heimburg P, Wegner G (1978) Sekundare hypertrophe obstruktive Kardiomyopathie bei Morbus Fabry. Med Welt 29:1851–1854
Hübner G, Gokel JM, Erdmann E, Scheidt W von, Christomanou H (1988) Isolierter Morbus Fabry des Herzens. Eine bisher unbekannte Variante des alpha-Galactosidasemangels A. Verh Dtsch Ges Pathol 72:580
Jensen E (1966) On the pathology of angiokeratoma corporis diffusum (Fabry). Acta Pathol Microbiol Scand 68:313–331
Kobayashi T, Kira J, Shinnoh N, Goto I, Yoshigoro K (1985) Fabry's disease with partially deficient hydrolysis of ceramid trihexoside. J Neurol Sci 67:179–185
Lou HOC (1966) A biochemical investigation of angiokeratoma coprporis diffusum. Acta Pathol Microbiol Scand 68:332–342
Machinami R (1972) Autopsy case of Fabry's disease. Acta Pathol Jpn 22:409–426
Mall G, Schwarz F, Zebe H, Kubler W (1985) Herzhypertrophie: Differential Diagnose an Endomokardialbiopsien. In: Mall G, Otto HF (eds) Herzhypertrophie. Springer, Berlin Heidelberg New York, pp 196–199
Mossard JM, Jossot G, Wolfe LS, Batzen-Schlager A, Stoebner P, Metzger H (1972) La coeur dans la maladie de Fabry. Arch Mal Coeur 65:495
Nilsson O, Svennerholm L (1982) Characterization and quantitative determination of gangliosides and neutral glycosphingolipids in human liver. J Lipid Res 23:327–334
Ogawa K, Abe T, Yoshimura K, Nagashima K, Nagashima T (1985) Cardiac accumulation of trihexosyl ceramide in a case with amyotrophic lateral sclerosis. Jpn J Exp Med 55:123–127
Romeo G, D'Urso M, Pisacane A, Blum E, DeFalco A, Ruffilli A (1975) Residual activity of alpha-galactosidase in Fabry's disease. Biochem Genet 13:615–628
Sakuraba H, Yanagawa Y, Igarashi T, Suzuki Y, Suzuki T, Watanabe T, Ieki K, Shimoda K, Yamanaka T (1986) Cardiovascular manifestations in Fabry's disease. Clin Genet 29:276–283
Yokoyama A, Yamazoe M, Shibata A (1987) A case of heterozygous Fabry's disease with a short PR interval and giant negative T waves. Br Heart J 57:296–299
Wynne J, Braunwald E (1988) The cardiomyopathies and myocarditides. In: Braunwald W (ed) Heart disease, 3rd edn. A textbook of cardiovascular medicine. Saunders, Philadelphia, p 1410
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Elleder, M., Bradová, V., Smíd, F. et al. Cardiocyte storage and hypertrophy as a sole manifestation of Fabry's disease. Vichows Archiv A Pathol Anat 417, 449–455 (1990). https://doi.org/10.1007/BF01606034
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01606034