Case Reports 263
Hunter H. (1977) XYY Males. Br. J. Psych. 131, 46S-77. Nielsen J. and Christiansen A L. (1974) Thirty Five Males with Double Y Chromosome. Psychol. Med. 4, 2S--37.
Noel B., Dupont J. P., Revil D., Dussu,yer I. and Quack B. (1974) the XYY syndrome: reality or myth? Clin. Gen. 5, 387-94. Sandberg A A, KoepfG. P., !sahara T. and Hauschka T. S. (1961) An XYY human male. Lancet 2, 48S--9.
Schiavi R. C., Theilgaard A, Owen D. R. and White D. (1984) Sex chromosome anomalies, hormones and aggressivity. Arch. Gen. Psychiat. 41 93-9. Theilgaard A (1983) Aggression and the XYY personality.Int. J. Law and Psychiat. 6, 413-21. Witkin H. A, Mednick S. A, Schulsinger F., Bakkestrom E., Christiansen K. 0., Goodenough D. R., Hirschorn K., Lundsteen C., Owen D. R., Philip J., Rubin D. B. and Stocking M. (1976) Criminality in XYY andXXY men. Science 193, 547-55.
3. Fabry's Disease - a rare cause of sudden death S SIVALOGANATHAN, MB BS DMJ (Clin. at Path.) Department of Forensic Medicine, St James's University Hospital, University of Leeds, Leeds ABSTRACT A case of Fabry's disease, an X-linked in-born error of metabolism, presenting as a sudden death in an elderly female, is reported, along with a review of the literature. The pathological fmdings of the cellular vacuolation and the characteristic inclusion bodies in the tissues are described.
INTRODUCTION
Fabry's disease is an in-born error of glycosphingolipid metabolism resulting from the defective activity of the lysosomal enzyme, alpha-galactosidase A. It is transmitted by an X-linked recessive gene. This condition was described in 1898, by Fabry and by Anderson independently. It leads to the accumulation of the neutral glycosphingolipid substrate, trihexosyl ceramide, in the lysosomes of the heart, kidney, brain (Desnick et al., 1989), blood vessels, lymph nodes and pancreas (Roth and Roth, 1978). It is usually recognized in the third and fourth decades of life. Being sexlinked, the manifestations in the heterozygous females, though documented (Rodriguez et al., 1985), are often less serious and less pronounced. The males are believed to have a significantly larger number of the characteristic inclusion bodies in their cells than females. Deaths in females are rare and usually due to the cardiac effects from this condition (Tsuda et al., 1988). Sudden or unexpected death is extremely rare; one such case is reported. CASE REPORT
The deceased was a 74-year-old married female, a resident of an elderly persons' home,
who had a history of 'rheumatic' fever as a child. She had had a gastrectomy for carcinoma of the stomach, and cholecystectomy in the past. She is believed to have had a stroke (cerebro-vascular accident) four years previously. She had been losing weight during the months prior to her death. This had been attributed to self-neglect. She was found dead in bed. There was no history of symptoms attributable to cardiovascular disease in the past. The post-mortem examination was performed 24 hours after death. She was 158cm tall and weighed only 33kg. There were no significant external marks apart from the surgical scars. The heart weighed 460gm. The chambers were dilated. Both ventricles were hypertrophied, the right ventricle being 7mm thick and the left 24mm. The myocardium had a mottled orange/yellow appearance suggestive of an infiltrative metabolic disease. The cut surface confirmed this infiltrative mottling involving the entire myocardium of both ventricles (Figure 1). In addition, there were scattered areas of focal scarring in the myocardium including a rather large area in the upper part of the septum. The cusps of the mitral valve showed marked myxoid change, but no evidence of rheumatic valve disease. The liver weighed 1000gm and showed no naked eye pathology. The kidneys weighed 240gm. The capsules stripped with difficulty to reveal smooth surfaces. The cut section showed mottling of the cortex and congested medulla.
264 Med. Sci. Law (1992) Vol. 32, No.3
Figure 1.Transverse section of the heart showing infiltrative mottling.
Figure 3. semi-thin section of myocardium stained with Methylene Blue and Azure II, x 400, showing Inclusion bodies (INC) in the vacuoles.
Semi-thin (0.5 micron) sections stained with 1 per cent methylene blue and azure II showed dense lamellar bodies in the vacuoles (Figure 3).
~-~
Figure 2. Section of the myocardium stained with H&E, x 100, showing the central vacuolation and hypertrophy.
The brain showed no evidence of any naked eye pathology, in particular there was no evidence of a previous stroke. The femoral marrow was fatty and showed little or no evidence of erythropoietic activity. HISTOLOGY In routine haematoxylin and eosin stained sections the heart showed enlarged myocardial cells with alteration of normal architecture. There was variation in size of the cells. The cells had large central vacuoles with the fibrils being pushed to the periphery (Figure 2). The myofibrils showed fragmentation. There was focal myocardial fibrosis, interstitial fibrosis and oedema. No significant changes were seen in the vascular endothelium.
Electron microscopy showed electron-dense inclusion bodies in the region of the vacuoles. These inclusions were in the form of spherical or oval concentric lamellar bodies. They were numerous and varied up to 3 microns in diameter (Figure 4). Histochemical examination showed PAS positive material only in frozen sections. Stains for lipids
Hunter H. (1977) XYY Males. Br. J. Psych. 131, 46S-77. Nielsen J. and Christiansen A L. (1974) Thirty Five Males with Double Y Chromosome. Psychol. Med. 4, 2S--37.
Noel B., Dupont J. P., Revil D., Dussu,yer I. and Quack B. (1974) the XYY syndrome: reality or myth? Clin. Gen. 5, 387-94. Sandberg A A, KoepfG. P., !sahara T. and Hauschka T. S. (1961) An XYY human male. Lancet 2, 48S--9.
Schiavi R. C., Theilgaard A, Owen D. R. and White D. (1984) Sex chromosome anomalies, hormones and aggressivity. Arch. Gen. Psychiat. 41 93-9. Theilgaard A (1983) Aggression and the XYY personality.Int. J. Law and Psychiat. 6, 413-21. Witkin H. A, Mednick S. A, Schulsinger F., Bakkestrom E., Christiansen K. 0., Goodenough D. R., Hirschorn K., Lundsteen C., Owen D. R., Philip J., Rubin D. B. and Stocking M. (1976) Criminality in XYY andXXY men. Science 193, 547-55.
3. Fabry's Disease - a rare cause of sudden death S SIVALOGANATHAN, MB BS DMJ (Clin. at Path.) Department of Forensic Medicine, St James's University Hospital, University of Leeds, Leeds ABSTRACT A case of Fabry's disease, an X-linked in-born error of metabolism, presenting as a sudden death in an elderly female, is reported, along with a review of the literature. The pathological fmdings of the cellular vacuolation and the characteristic inclusion bodies in the tissues are described.
INTRODUCTION
Fabry's disease is an in-born error of glycosphingolipid metabolism resulting from the defective activity of the lysosomal enzyme, alpha-galactosidase A. It is transmitted by an X-linked recessive gene. This condition was described in 1898, by Fabry and by Anderson independently. It leads to the accumulation of the neutral glycosphingolipid substrate, trihexosyl ceramide, in the lysosomes of the heart, kidney, brain (Desnick et al., 1989), blood vessels, lymph nodes and pancreas (Roth and Roth, 1978). It is usually recognized in the third and fourth decades of life. Being sexlinked, the manifestations in the heterozygous females, though documented (Rodriguez et al., 1985), are often less serious and less pronounced. The males are believed to have a significantly larger number of the characteristic inclusion bodies in their cells than females. Deaths in females are rare and usually due to the cardiac effects from this condition (Tsuda et al., 1988). Sudden or unexpected death is extremely rare; one such case is reported. CASE REPORT
The deceased was a 74-year-old married female, a resident of an elderly persons' home,
who had a history of 'rheumatic' fever as a child. She had had a gastrectomy for carcinoma of the stomach, and cholecystectomy in the past. She is believed to have had a stroke (cerebro-vascular accident) four years previously. She had been losing weight during the months prior to her death. This had been attributed to self-neglect. She was found dead in bed. There was no history of symptoms attributable to cardiovascular disease in the past. The post-mortem examination was performed 24 hours after death. She was 158cm tall and weighed only 33kg. There were no significant external marks apart from the surgical scars. The heart weighed 460gm. The chambers were dilated. Both ventricles were hypertrophied, the right ventricle being 7mm thick and the left 24mm. The myocardium had a mottled orange/yellow appearance suggestive of an infiltrative metabolic disease. The cut surface confirmed this infiltrative mottling involving the entire myocardium of both ventricles (Figure 1). In addition, there were scattered areas of focal scarring in the myocardium including a rather large area in the upper part of the septum. The cusps of the mitral valve showed marked myxoid change, but no evidence of rheumatic valve disease. The liver weighed 1000gm and showed no naked eye pathology. The kidneys weighed 240gm. The capsules stripped with difficulty to reveal smooth surfaces. The cut section showed mottling of the cortex and congested medulla.
264 Med. Sci. Law (1992) Vol. 32, No.3
Figure 1.Transverse section of the heart showing infiltrative mottling.
Figure 3. semi-thin section of myocardium stained with Methylene Blue and Azure II, x 400, showing Inclusion bodies (INC) in the vacuoles.
Semi-thin (0.5 micron) sections stained with 1 per cent methylene blue and azure II showed dense lamellar bodies in the vacuoles (Figure 3).
~-~
Figure 2. Section of the myocardium stained with H&E, x 100, showing the central vacuolation and hypertrophy.
The brain showed no evidence of any naked eye pathology, in particular there was no evidence of a previous stroke. The femoral marrow was fatty and showed little or no evidence of erythropoietic activity. HISTOLOGY In routine haematoxylin and eosin stained sections the heart showed enlarged myocardial cells with alteration of normal architecture. There was variation in size of the cells. The cells had large central vacuoles with the fibrils being pushed to the periphery (Figure 2). The myofibrils showed fragmentation. There was focal myocardial fibrosis, interstitial fibrosis and oedema. No significant changes were seen in the vascular endothelium.
Electron microscopy showed electron-dense inclusion bodies in the region of the vacuoles. These inclusions were in the form of spherical or oval concentric lamellar bodies. They were numerous and varied up to 3 microns in diameter (Figure 4). Histochemical examination showed PAS positive material only in frozen sections. Stains for lipids
