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Niemann-Pick Disease (Type C)
NIEMANN-PICK DISEASE ( T Y P E C) HlSTOPATHOLOGY AND ULTRASTRUCTURE J A R E D M . E M E R Y , M.D., A N D W I L L I A M R. G R E E N ,
M.D.
Baltimore, Maryland D A L E S. H U F F ,
M.D.
Philadelphia, Pennsylvania AND H O W A R D R. S L O A N ,
M.D.
Bethesda, Maryland
Niemann-Pick disease, an inherited sphingolipid storage disease with autosomal recessive transmission,1 was recognized as a distinct entity about a half-century ago.2'3 More recently, Crocker and Färber4-5 recog nized several different forms of the disease, and classified them as groups A through D. Type A, the classical Niemann-Pick dis ease, begins with hepatosplenomegaly and psychomotor deterioration in early infancy, frequently shows cherry red spots of the maculae, and usually results in death by the age of two years. Type B is a benign form with hepatosplenomegaly but no central ner vous system (CNS) symptoms. No macular lesions have been found in well-documented cases of Type B Niemann-Pick disease. The life span in this form may be normal. Type C shows moderate hepatosplenomegaly, on set of psychomotor deterioration in late in fancy, and occasionally the cherry red spots ; death occurs between the ages of three and six years. Type D, the "Nova Scotian" vari ant, also has hepatosplenomegaly; CNS symptoms appear in early to mid childhood, but cherry red spots have not been observed.
Death usually occurs between the ages of 12 and 20 years. Although all four types have sphingomyelin storage, this abnormality is most marked in Types A and B and a defi ciency of the enzyme sphingomyelinase has been demonstrated only in Types A and B. The ocular histopathology described in four cases6-9 reported as being examples of Type A, or classical, Niemann-Pick disease revealed ballooned lipid-laden retinal gan glion cells. Other findings included vacuo lated cells in the inner and outer nuclear lay ers, edema of the outer plexiform layer, and more vacuolated cells within the choroid and sciera. The optic nerve showed lipid deposi tion within glial cells. As far as we have been able to determine, the ocular tissues in Type-B Niemann-Pick disease have not been studied. A recent case report by Rabinowicz and others10 of a juvenile form of Niemann-Pick disease (Type D according to the authors, but Type C in our opinion, since the patient did not have a Nova Scotian ancestry) dem onstrated ballooned retinal ganglion cells de spite a history of apparently normal visual acuity and a normal fundus examination. Sudan black B stain for lipid was described From the Eye Pathology Laboratory of the Wilmer Institute of the Johns Hopkins Hospital (Drs. as weakly positive. Emery and Green), Baltimore, Maryland, St. To our knowledge, electronmicroscopic Christopher's Hospital for Children (Dr. Huff), studies have not previously been done on the Philadelphia, Pennsylvania, and the National Heart and Lung Institute, Bethesda, Maryland (Dr. eyes of any patient with Niemann-Pick dis Sloan). ease. This paper presents the histopathology Reprint requests to William R. Green, M.D., Eye and ultrastructure of the eye in a case of Pathology Laboratory, Johns Hopkins Hospital, Type-C Niemann-Pick disease. 601 N. Broadway, Baltimore, Maryland 21205. 1144
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C A S E REPORT
This white boy was eight years old when he was examined initially at the National Institute of Health. He had a five-year-old brother with sple nomegaly and foam cells in his bone marrow, and a normal 11-year-old sister. An uncle died at the age of 10 years with convulsions. The patient was the product of a normal preg nancy and delivery. At the age of six weeks sple nomegaly was noted, and bone marrow biopsy re vealed foamy histiocytes. Growth and development were normal until the age of five years, when pro gressive psychomotor deterioration began, with right-sided seizures appearing at the age of seven years. When he was eight, evaluation at the National Institutes of Health revealed grossly nor mal vision. The fundi were carefully examined (by experienced observers) and found to be entirely within normal limits. No ocular and specifically no scierai abnormalities were noted. Liver biopsy re vealed large foamy macrophages, probably Kupffer cells, in the sinusoids and along the portal track; these foamy cells contained material that stained strongly with PAS and Schultz stain for choles terol and weakly with the Baker-hematoxylin stain for phospholipids. These findings led to a diagnosis of lipid storage disease of unknown etiology. By the age of 11, the patient could not walk, talk, or feed himself, and he died of undetermined cause. Autopsy performed at St. Christopher's Hospital for Children, in Philadelphia revealed marked hepatosplenomegaly (Fig. 1). Large foamy reticuloendothelial cells were present in the liver and spleen, and stained positively for lipid with oil-red-0 (Figs. 2 and 3), Sudan black, Baker's, Schultz, PAS, and Rhinehart. The thymus and lymph nodes showed an intense yellow coloration grossly, and sections showed foamy cells which stained posi tively for lipid with these same stains (Figs. 4 and 5). The material in the foamy macrophages stained positively with stains for fat in frozen sections as well as in formalin-fixed, paraffin-embedded tissues. The lungs, bone marrow, kidneys, tonsils, small in testines, colon, esophagus and heart were infiltrated by similar foamy macrophages. The brain showed numerous swollen foamy neurons, which did not, however, stain strongly for lipid (Fig. 6). The pe ripheral autonomie ganglion cells showed changes similar to those in the central nervous system. The diagnosis of Niemann-Pick disease was con firmed by the fact that the spleen contained twice the normal level of phospholipid, more than five times the normal value of sphingomyelin, and over three times the normal level of cholesterol (Table 1). The sphingomyelin cleaving enzyme activity in the patient's liver was 7.8 as compared with a nor mal range of 4.4-11.1. MATERIALS AND METHODS
The eyes were enucleated shortly after death and were fixed in 10% formalin solu-
Fig. 1 (Emery and associates). Hepatosplenomegaly in Type-C Niemann-Pick disease.
tion. One globe was paraffin-embedded for routine hematoxylin-eosin staining of serial sections through the pupil-optic nerve axis. Special stains included PAS, Sudan black B, oil-red-O, Landing's (for phospholipid), Verhoeff-van Gieson, and Masson's trichrome. For electronmicroscopic study, diced sam ples of all tissues of the other eye were washed in phosphate buffer solution, and were then individually fixed in 2 % osmium tetroxide with phosphate buffer for two and one-half hours. The tissue was then dehy drated and embedded in epoxy resin (Araldite). Thick sections (about 2μ) from this material were stained with toluidine blue and used to select the areas for electronmicroscopy. Ultrathin sections were prepared on an ultramicrotome (Porter-Blum MT-2), stained with lead citrate and uranyl acetate, and studied in electronmicroscopes (RCA model EMU-3G and E M U - 3 H ) .
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Fig. 2 (Emery and associates). Liver. Numerous large foamy reticuloendothelial cells (arrows) (hematoxylin and eosin, χ500).
RESULTS
Gross findings—Gross pathologic exami nation of the eyes revealed triangular patches of thinned translucent sciera adja cent to the limbus in the interpalpebral fis sure zone in both eyes (Fig. 7). No other ab normalities were noted. Microscopy—The only definite abnor mality was the unusual scierai tissue noted above. In routine hematoxylin-eosin sections studied by light microscopy, the region cor responding to the grossly observed translu cent sciera was unremarkable except for un usual compactness of its collagen bundles; this region stained intensely red by the Masson technique (Fig. 8). By electronmicroscopy, this area was composed of lamellae of
densely packed collagen fibrils of uniform cross-sectional diameter equaling approxi mately 30 nm (Fig. 9 ) . All other tissues of the globe were normal by light microscopy, including the optic nerve and retina, whose outer plexiform layer had an edematous appearance (Fig. 10) from postmortem autolysis. Retinal gan glion cells did not stain with PAS, Sudan black B, Landing's stain for phospholipids or with oil-red-O. Optic-nerve myelin stained normally with Verhoeff-van Gieson stain. Tissues examined and found normal by electronmicroscopy include: cornea, ciliary body, retina, choroid, optic nerve and sciera (except for the patches of translucent sciera noted above) ; retinal ganglion cells showed
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Fig. 3 (Emery and associates). Spleen. Foamy distended reticuloendothelial cells (arrows) (hematoxylin and eosin, χ500). no evidence of "zebra bodies," membranous cytoplasmic bodies, or other abnormal inclu sions. COMMENT
Ocular histopathologic and ultrastructural studies in this case of Type-C Niemann-Pick disease reveal unusual, bilateral cornea-like patches of translucent sciera in the area of the interpalpebral fissure. The ultrastruc tural appearance of this tissue is characteris tic of cornea, with lamellae of closely packed collagen fibrils of uniform cross-sectional di ameter of 30 nm ; sciera shows a more hap hazard arrangement of its less-compact col lagen fibrils, whose diameters vary from 30 to 330 nm. An apparent extension of corneal
tissue into the sciera by about 2 mm has been observed.13"15 The present case appears to be unique in its extensive (4-6 mm) replace ment of scierai tissue by cornea adjacent to the limbus nasally and temporally in both eyes. The relation of this corneo-sclera anomaly to the underlying disease process is unclear. In addition, we found a cystic, or edematous, appearance of the outer plexiform layer of the retina similar to that previously described in Type-A Niemann-Pick dis ease.6"9 In our opinion, this finding is nothing more than postmortem autolysis. Unlike the findings of Rabinowicz and associates10 in a case of Type-C Niemann-Pick disease, we observed no convincing histochemical evi-
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Fig. 4 (Emery and associates). Lymph node. Foamy reticuloendothelial cells (arrows) (hematoxylin and eosin, XSOO).
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Fig. S (Emery and associates). Lymph node. Foamy reticuloendothelial cells stain positively for lipid (arrows) (oil-red-O, χ500).
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Fig. 6 (Emery and associates). Cerebral cortex. Swollen foamy neurons (hematoxylin and eosin, XSOO).
TABLE 1 TISSUE LIPID CONCENTRATIONS
Tissue
Source
Phospholipids*
Sphingomyelin*
Cholesterol*
Liver
Present case Normalst Present case Normalst
40.2 25.1 ±2.7 33.2 15.0±1.9
6.2 1.8±0.4 12.4 2.4±0.4
13.5 3.9±0.8 16.8 5.1±0.4
Spleen * In mg/g wet tissue, t Means ±S.D.
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Fig. 7 (Emery and associates). Triangular patches of thinned translucent sciera adjacent to the limbus, both eyes.
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Fig. 8 (Emery and associates). Region of translucent sciera (arrows) adjacent to limbus, with compact collagen lamellae (Masson, xSO).
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Fig. 9 (Emery and associates). Translucent sciera. Lamellae of densely packed collagen fibrils of rela tively uniform cross-sectional diameter (electromicrograph, χ26,400).
dence for lipid storage within retinal gan glion cells, a finding borne out by our ultrastructural studies. These differences are consistent with the variable clinical, biochemical, and pathologic findings among the reported cases of Type-C Niemann-Pick disease. Indeed, this hetero geneity is so great that it suggests that T y p e C really represents a group of diseases, rather than a specific entity. SUMMARY
U n u s u a l large patches of cornea-like scierai tissue were present adjacent to the limbus nasally and temporally in both eyes in a case of Niemann-Pick disease ( T y p e C ) . T h e relation between the scierai anomaly and
Niemann-Pick disease is unclear. I n contrast to the one previous ocular histopathologic re port of T y p e - C Niemann-Pick disease, no evidence of lipid storage within retinal gan glion cells was found. T h i s negative finding was confirmed by ultrastructural studies in this case. ACKNOWLEDGMENT
John H. Yardley, M.D., provided technical assis tance and laboratory facilities for the electromicroscope portion of this work. REFERENCES
1. Frederickson, D. S., and Sloan, H. R. : Sphingomyelin lipidoses : Niemann-Pick disease. In Stanbury, J. B., Wygaarden, J. B., and Frederickson, D. S. (eds.) : The Metabolic Basis of Inherited Diseases. New York, McGraw-Hill, 1971, p. 783.
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Fig. 10 (Emery and associates). Retina. Cystic or edematous appearance of outer plexiform layer from autolysis (hematoxylin and eosin, X250). 2. Niemann, A. : Ein unbekanntes Krankheits bild. Jahrb. Kinderheilk. 79:1, 1914. 3. Pick, L. : Niemann-Pick's disease and other forms of so-called xanthomatosis. Am. J. Med. Sei. 185:601,1933. 4. Crocker, A. C. : The cerebral defect in TaySachs disease and Niemann-Pick disease. J. Neurochem. 7:69, 1961. 5. Crocker, A. C, and Farber, S.: NiemannPick's disease: A review of 18 patients. Medicine 37:1, 1958. 6. Goldstein, I., and Wexler, D. : NiemannPick's disease with cherry red spots in the macula : Ocular pathology. Arch. Ophth. 5:704, 1931. 7. Rintelen, F. : Die Histopathologie der Argenhintergrunds-veranderungen bei Niemann-Pickscher Lipiodose. Arch. Augenheilk. 109:332, 1936. 8. Didion, H. : Die anatomische Veränderungen des Augenhintergrundes bei der Niemann-Pickschen Krankheit. Klin. Mbl. Angenheilk. 116:131, 1950. 9. Larsen, H., and Ehlers, N. : Ocular manifes
tations in Tay-Sachs' and Niemann-Pick's diseases. Acta Ophth. (Kbh) 43:285, 1965. 10. Rabinowicz, T., Klein, D., and Tchicaloff, M. : Juvenile form of Niemann-Pick disease. Path. Europ. 3:154, 1968. 11. Norman, R. M., Forrester, R. M., and Tingey, A. H. : The juvenile form of Niemann-Pick disease. Arch. Dis. Child. 42:91, 1967. 12. Oppenheimer, D. R., Norman, R. M., Tingey, A. H., and Aherne, W. A. : Histological and chemi cal findings in juvenile Niemann-Pick disease. J. Neurol. Sei. 5:575, 1967. 13. Kraupa, E. : Fehlen des Lederhautbandes in Sichelform als Abweichung vom gewohnlichen Verhalten der Hornhaut-Lederhautgrenze. Klin. Mbl. Augenheilk. 64:698, 1920. 14. Kayser, B. : Ueber Embryotoxon corneae posterius nebst einem Befund von persistierenden Resten der Membrana capsulo-pupillaris lentis. Klin. Mbl. Augenheilk. 68:82,1922. 15. Ascher, K. W. : Partial coloboma of the scleral-limbus zone with visible Schlemm's canal. Am. J. Ophth. 24:615, 1941.
M.D.
Baltimore, Maryland D A L E S. H U F F ,
M.D.
Philadelphia, Pennsylvania AND H O W A R D R. S L O A N ,
M.D.
Bethesda, Maryland
Niemann-Pick disease, an inherited sphingolipid storage disease with autosomal recessive transmission,1 was recognized as a distinct entity about a half-century ago.2'3 More recently, Crocker and Färber4-5 recog nized several different forms of the disease, and classified them as groups A through D. Type A, the classical Niemann-Pick dis ease, begins with hepatosplenomegaly and psychomotor deterioration in early infancy, frequently shows cherry red spots of the maculae, and usually results in death by the age of two years. Type B is a benign form with hepatosplenomegaly but no central ner vous system (CNS) symptoms. No macular lesions have been found in well-documented cases of Type B Niemann-Pick disease. The life span in this form may be normal. Type C shows moderate hepatosplenomegaly, on set of psychomotor deterioration in late in fancy, and occasionally the cherry red spots ; death occurs between the ages of three and six years. Type D, the "Nova Scotian" vari ant, also has hepatosplenomegaly; CNS symptoms appear in early to mid childhood, but cherry red spots have not been observed.
Death usually occurs between the ages of 12 and 20 years. Although all four types have sphingomyelin storage, this abnormality is most marked in Types A and B and a defi ciency of the enzyme sphingomyelinase has been demonstrated only in Types A and B. The ocular histopathology described in four cases6-9 reported as being examples of Type A, or classical, Niemann-Pick disease revealed ballooned lipid-laden retinal gan glion cells. Other findings included vacuo lated cells in the inner and outer nuclear lay ers, edema of the outer plexiform layer, and more vacuolated cells within the choroid and sciera. The optic nerve showed lipid deposi tion within glial cells. As far as we have been able to determine, the ocular tissues in Type-B Niemann-Pick disease have not been studied. A recent case report by Rabinowicz and others10 of a juvenile form of Niemann-Pick disease (Type D according to the authors, but Type C in our opinion, since the patient did not have a Nova Scotian ancestry) dem onstrated ballooned retinal ganglion cells de spite a history of apparently normal visual acuity and a normal fundus examination. Sudan black B stain for lipid was described From the Eye Pathology Laboratory of the Wilmer Institute of the Johns Hopkins Hospital (Drs. as weakly positive. Emery and Green), Baltimore, Maryland, St. To our knowledge, electronmicroscopic Christopher's Hospital for Children (Dr. Huff), studies have not previously been done on the Philadelphia, Pennsylvania, and the National Heart and Lung Institute, Bethesda, Maryland (Dr. eyes of any patient with Niemann-Pick dis Sloan). ease. This paper presents the histopathology Reprint requests to William R. Green, M.D., Eye and ultrastructure of the eye in a case of Pathology Laboratory, Johns Hopkins Hospital, Type-C Niemann-Pick disease. 601 N. Broadway, Baltimore, Maryland 21205. 1144
VOL. 74, NO. 6
NIEMANN-PICK DISEASE (TYPE C)
1145
C A S E REPORT
This white boy was eight years old when he was examined initially at the National Institute of Health. He had a five-year-old brother with sple nomegaly and foam cells in his bone marrow, and a normal 11-year-old sister. An uncle died at the age of 10 years with convulsions. The patient was the product of a normal preg nancy and delivery. At the age of six weeks sple nomegaly was noted, and bone marrow biopsy re vealed foamy histiocytes. Growth and development were normal until the age of five years, when pro gressive psychomotor deterioration began, with right-sided seizures appearing at the age of seven years. When he was eight, evaluation at the National Institutes of Health revealed grossly nor mal vision. The fundi were carefully examined (by experienced observers) and found to be entirely within normal limits. No ocular and specifically no scierai abnormalities were noted. Liver biopsy re vealed large foamy macrophages, probably Kupffer cells, in the sinusoids and along the portal track; these foamy cells contained material that stained strongly with PAS and Schultz stain for choles terol and weakly with the Baker-hematoxylin stain for phospholipids. These findings led to a diagnosis of lipid storage disease of unknown etiology. By the age of 11, the patient could not walk, talk, or feed himself, and he died of undetermined cause. Autopsy performed at St. Christopher's Hospital for Children, in Philadelphia revealed marked hepatosplenomegaly (Fig. 1). Large foamy reticuloendothelial cells were present in the liver and spleen, and stained positively for lipid with oil-red-0 (Figs. 2 and 3), Sudan black, Baker's, Schultz, PAS, and Rhinehart. The thymus and lymph nodes showed an intense yellow coloration grossly, and sections showed foamy cells which stained posi tively for lipid with these same stains (Figs. 4 and 5). The material in the foamy macrophages stained positively with stains for fat in frozen sections as well as in formalin-fixed, paraffin-embedded tissues. The lungs, bone marrow, kidneys, tonsils, small in testines, colon, esophagus and heart were infiltrated by similar foamy macrophages. The brain showed numerous swollen foamy neurons, which did not, however, stain strongly for lipid (Fig. 6). The pe ripheral autonomie ganglion cells showed changes similar to those in the central nervous system. The diagnosis of Niemann-Pick disease was con firmed by the fact that the spleen contained twice the normal level of phospholipid, more than five times the normal value of sphingomyelin, and over three times the normal level of cholesterol (Table 1). The sphingomyelin cleaving enzyme activity in the patient's liver was 7.8 as compared with a nor mal range of 4.4-11.1. MATERIALS AND METHODS
The eyes were enucleated shortly after death and were fixed in 10% formalin solu-
Fig. 1 (Emery and associates). Hepatosplenomegaly in Type-C Niemann-Pick disease.
tion. One globe was paraffin-embedded for routine hematoxylin-eosin staining of serial sections through the pupil-optic nerve axis. Special stains included PAS, Sudan black B, oil-red-O, Landing's (for phospholipid), Verhoeff-van Gieson, and Masson's trichrome. For electronmicroscopic study, diced sam ples of all tissues of the other eye were washed in phosphate buffer solution, and were then individually fixed in 2 % osmium tetroxide with phosphate buffer for two and one-half hours. The tissue was then dehy drated and embedded in epoxy resin (Araldite). Thick sections (about 2μ) from this material were stained with toluidine blue and used to select the areas for electronmicroscopy. Ultrathin sections were prepared on an ultramicrotome (Porter-Blum MT-2), stained with lead citrate and uranyl acetate, and studied in electronmicroscopes (RCA model EMU-3G and E M U - 3 H ) .
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Fig. 2 (Emery and associates). Liver. Numerous large foamy reticuloendothelial cells (arrows) (hematoxylin and eosin, χ500).
RESULTS
Gross findings—Gross pathologic exami nation of the eyes revealed triangular patches of thinned translucent sciera adja cent to the limbus in the interpalpebral fis sure zone in both eyes (Fig. 7). No other ab normalities were noted. Microscopy—The only definite abnor mality was the unusual scierai tissue noted above. In routine hematoxylin-eosin sections studied by light microscopy, the region cor responding to the grossly observed translu cent sciera was unremarkable except for un usual compactness of its collagen bundles; this region stained intensely red by the Masson technique (Fig. 8). By electronmicroscopy, this area was composed of lamellae of
densely packed collagen fibrils of uniform cross-sectional diameter equaling approxi mately 30 nm (Fig. 9 ) . All other tissues of the globe were normal by light microscopy, including the optic nerve and retina, whose outer plexiform layer had an edematous appearance (Fig. 10) from postmortem autolysis. Retinal gan glion cells did not stain with PAS, Sudan black B, Landing's stain for phospholipids or with oil-red-O. Optic-nerve myelin stained normally with Verhoeff-van Gieson stain. Tissues examined and found normal by electronmicroscopy include: cornea, ciliary body, retina, choroid, optic nerve and sciera (except for the patches of translucent sciera noted above) ; retinal ganglion cells showed
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Fig. 3 (Emery and associates). Spleen. Foamy distended reticuloendothelial cells (arrows) (hematoxylin and eosin, χ500). no evidence of "zebra bodies," membranous cytoplasmic bodies, or other abnormal inclu sions. COMMENT
Ocular histopathologic and ultrastructural studies in this case of Type-C Niemann-Pick disease reveal unusual, bilateral cornea-like patches of translucent sciera in the area of the interpalpebral fissure. The ultrastruc tural appearance of this tissue is characteris tic of cornea, with lamellae of closely packed collagen fibrils of uniform cross-sectional di ameter of 30 nm ; sciera shows a more hap hazard arrangement of its less-compact col lagen fibrils, whose diameters vary from 30 to 330 nm. An apparent extension of corneal
tissue into the sciera by about 2 mm has been observed.13"15 The present case appears to be unique in its extensive (4-6 mm) replace ment of scierai tissue by cornea adjacent to the limbus nasally and temporally in both eyes. The relation of this corneo-sclera anomaly to the underlying disease process is unclear. In addition, we found a cystic, or edematous, appearance of the outer plexiform layer of the retina similar to that previously described in Type-A Niemann-Pick dis ease.6"9 In our opinion, this finding is nothing more than postmortem autolysis. Unlike the findings of Rabinowicz and associates10 in a case of Type-C Niemann-Pick disease, we observed no convincing histochemical evi-
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Fig. 4 (Emery and associates). Lymph node. Foamy reticuloendothelial cells (arrows) (hematoxylin and eosin, XSOO).
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Fig. S (Emery and associates). Lymph node. Foamy reticuloendothelial cells stain positively for lipid (arrows) (oil-red-O, χ500).
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Fig. 6 (Emery and associates). Cerebral cortex. Swollen foamy neurons (hematoxylin and eosin, XSOO).
TABLE 1 TISSUE LIPID CONCENTRATIONS
Tissue
Source
Phospholipids*
Sphingomyelin*
Cholesterol*
Liver
Present case Normalst Present case Normalst
40.2 25.1 ±2.7 33.2 15.0±1.9
6.2 1.8±0.4 12.4 2.4±0.4
13.5 3.9±0.8 16.8 5.1±0.4
Spleen * In mg/g wet tissue, t Means ±S.D.
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Fig. 7 (Emery and associates). Triangular patches of thinned translucent sciera adjacent to the limbus, both eyes.
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Fig. 8 (Emery and associates). Region of translucent sciera (arrows) adjacent to limbus, with compact collagen lamellae (Masson, xSO).
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Fig. 9 (Emery and associates). Translucent sciera. Lamellae of densely packed collagen fibrils of rela tively uniform cross-sectional diameter (electromicrograph, χ26,400).
dence for lipid storage within retinal gan glion cells, a finding borne out by our ultrastructural studies. These differences are consistent with the variable clinical, biochemical, and pathologic findings among the reported cases of Type-C Niemann-Pick disease. Indeed, this hetero geneity is so great that it suggests that T y p e C really represents a group of diseases, rather than a specific entity. SUMMARY
U n u s u a l large patches of cornea-like scierai tissue were present adjacent to the limbus nasally and temporally in both eyes in a case of Niemann-Pick disease ( T y p e C ) . T h e relation between the scierai anomaly and
Niemann-Pick disease is unclear. I n contrast to the one previous ocular histopathologic re port of T y p e - C Niemann-Pick disease, no evidence of lipid storage within retinal gan glion cells was found. T h i s negative finding was confirmed by ultrastructural studies in this case. ACKNOWLEDGMENT
John H. Yardley, M.D., provided technical assis tance and laboratory facilities for the electromicroscope portion of this work. REFERENCES
1. Frederickson, D. S., and Sloan, H. R. : Sphingomyelin lipidoses : Niemann-Pick disease. In Stanbury, J. B., Wygaarden, J. B., and Frederickson, D. S. (eds.) : The Metabolic Basis of Inherited Diseases. New York, McGraw-Hill, 1971, p. 783.
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Fig. 10 (Emery and associates). Retina. Cystic or edematous appearance of outer plexiform layer from autolysis (hematoxylin and eosin, X250). 2. Niemann, A. : Ein unbekanntes Krankheits bild. Jahrb. Kinderheilk. 79:1, 1914. 3. Pick, L. : Niemann-Pick's disease and other forms of so-called xanthomatosis. Am. J. Med. Sei. 185:601,1933. 4. Crocker, A. C. : The cerebral defect in TaySachs disease and Niemann-Pick disease. J. Neurochem. 7:69, 1961. 5. Crocker, A. C, and Farber, S.: NiemannPick's disease: A review of 18 patients. Medicine 37:1, 1958. 6. Goldstein, I., and Wexler, D. : NiemannPick's disease with cherry red spots in the macula : Ocular pathology. Arch. Ophth. 5:704, 1931. 7. Rintelen, F. : Die Histopathologie der Argenhintergrunds-veranderungen bei Niemann-Pickscher Lipiodose. Arch. Augenheilk. 109:332, 1936. 8. Didion, H. : Die anatomische Veränderungen des Augenhintergrundes bei der Niemann-Pickschen Krankheit. Klin. Mbl. Angenheilk. 116:131, 1950. 9. Larsen, H., and Ehlers, N. : Ocular manifes
tations in Tay-Sachs' and Niemann-Pick's diseases. Acta Ophth. (Kbh) 43:285, 1965. 10. Rabinowicz, T., Klein, D., and Tchicaloff, M. : Juvenile form of Niemann-Pick disease. Path. Europ. 3:154, 1968. 11. Norman, R. M., Forrester, R. M., and Tingey, A. H. : The juvenile form of Niemann-Pick disease. Arch. Dis. Child. 42:91, 1967. 12. Oppenheimer, D. R., Norman, R. M., Tingey, A. H., and Aherne, W. A. : Histological and chemi cal findings in juvenile Niemann-Pick disease. J. Neurol. Sei. 5:575, 1967. 13. Kraupa, E. : Fehlen des Lederhautbandes in Sichelform als Abweichung vom gewohnlichen Verhalten der Hornhaut-Lederhautgrenze. Klin. Mbl. Augenheilk. 64:698, 1920. 14. Kayser, B. : Ueber Embryotoxon corneae posterius nebst einem Befund von persistierenden Resten der Membrana capsulo-pupillaris lentis. Klin. Mbl. Augenheilk. 68:82,1922. 15. Ascher, K. W. : Partial coloboma of the scleral-limbus zone with visible Schlemm's canal. Am. J. Ophth. 24:615, 1941.