Pediatric Pathology
ISSN: 0277-0938 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ipdp17
Leukocyte Inclusions in Glycogen Storage Disease, Type IV To cite this article: (1992) Leukocyte Inclusions in Glycogen Storage Disease, Type IV, Pediatric Pathology, 12:6, 903-905, DOI: 10.3109/15513819209024249 To link to this article: http://dx.doi.org/10.3109/15513819209024249
Published online: 09 Jul 2009.
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Date: 30 March 2016, At: 05:12
LETTER TO THE EDITOR
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LEUKOCYTE INCLUSIONS IN GLYCOGEN STORAGE DISEASE. TYPE IV The existence of some metabolic disorders, including glycogen storage disease type 11, can be adduced from careful examination of the peripheral blood film in the form of vacuoles or inclusions in the leukocytes. We wish to record the observation of periodic acid-Schiff (PAS)-positive, diastase-resistant inclusions in the neutrophils and lymphocytes of a patient who had glycogen storage disease type IV, a condition that is not included in the lists of morphologic clues to be found in the blood (1). Glycogen storage disease type IV (Andersen disease, McKusick, 23250), a deficiency of the branching enzyme, results in the intracellular deposition of a relatively insoluble amylopectin-like material, seen in many organs but most prominently in liver, heart, muscle, central nervous system, and skin (2, 3). The intracytoplasmic inclusions stain with PAS and resist diastase digestion but are vulnerable to pectinase digestion (2). The inclusions characteristically stain with colloidal iron and are said to be variably blue to purple-brown when reacted with iodine (2). The inclusions are antigenically similar to Lafora bodies (4), suggesting that they are ubiquitinated (5). Although the enzyme defect is readily detectable in leukocytes ( 6 ) , illustrations of leukocyte inclusions are not recorded.. A 32-month-old boy underwent liver transplantation for cirrhosis caused by enzymatically confirmed glycogen storage disease type IV. The liver contained the characteristic inclusions in the hepatocytes. Portal macrophages and macrophages in a hilar lymph node contained complex ceroid (lipochrome) that had very similar tinctorial properties to the hepatocellular inclusions, suggesting that the ingested material was derived from the inclusions. No abnormality was detected, even in retrospect, on the Wright-Giemsastained peripheral blood smear; however, when the blood films made from EDTA-collected blood samples were stained with PAS, multiple angular inclusions of varying shape and size were seen in 16% of the neutrophils. These irregular cytoplasmic inclusions, like those elsewhere in the body, resisted digestion by diastase (Fig. 1A). The inclusions gave a dark brown color when treated with Lugol’s iodine (Fig. lB), indicating their similarity to the somatic inclusions (2). A rare lymphocyte had more regularly distributed and round PASpositive, diastase-resistant globules (Fig. 1C). Electron microscopy using standard techniques on a glutaraldehyde-fixed buffy coat revealed a lymphocyte with a large, round membrane-bound cytoplasmic inclusion containing short, occasionally branched, randomly oriented fdaments (Fig. 2). The filaments measured 6-8 nm in diameter, characteristic Pediatric Patholoo, 12:903-905, 1992 Copyright @ 1992 by Hemisphere Publishing Corporation
903
Downloaded by [69.162.139.9] at 05:12 30 March 2016
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LETTER TO THE EDITOR
of the amylopectin-like material found in glycogen storage disease type IV. A number of neutrophils contained mottled, medium dense, membrane-bound cytoplasmic masses of amorphous material resembling ceroid but without the characteristic filamentous structure of the amylopectin-like material. Cytoplasmic inclusions with characteristic staining qualities can be found in the neutrophils and lymphocytes in glycogen storage disease type IV. Whereas the lymphocyte inclusions are typical and resemble those found in other organs by ultrastructural study, the more obvious neutrophil inclusions may represent altered and phagocytosed material derived from the amylopectin-like inclusions similar to that found in hepatic portal and hilar lymph node macrophages. Fibroblasts from the patient and lymphocytes from his parents were banked at the NIGMS Cell Repository, Cornell Institute for Medical Research, Camden, NJ (GM12131, patient; GM12136, mother; GM12137, father).
Lila Penchansky, MD Rocco M. Agostini, BS Ronald Jaffe, MD Department o f Pathology, University o f Pittsburgh and Children 5 Hospital o f Pittsburgh Main Tower Rm. 5938 Pittsburgh, Pennsylvania 15213 Address reprint requests to first author at address above.
FIGURE 1. Peripheral blood smear from a patient with glycogen storage disease, type IV. X 1000. (A) A neutrophil contains irregular clumps of PAS-positive material that resists diastase digestion. (B) When reacted with Lugol's iodine the cytoplasmic inclusions give a brown color. Though not specific, the reaction is characteristic. (C) A lymphocyte has a ring of PAS-positive, diastase-resistant granules in the cytoplasm.
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LETTER TO THE EDITOR
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FIGURE 2. (A) A lymphocyte has a large, rounded, membrane-bound inclusion (arrow). Uranyl acetatelead citrate, X 19,500. (B) A higher-power image of the inclusion reveals short, occasionally branched, 6-8nm filaments consistent with the amylopectin-like material of glycogenosis IV. Uranyl acetate-lead citrate, x91,ooo.
REFERENCES 1. Kolodny EH, Boustany R M . Storage diseases of the reticuloendothelial system. In: Nathan DG, Oski FA, eds. Hematology of Infancy and Childhood. 3rd ed. Philadelphia, W. B. Saunders, 1987;1217. 2. Schochet SS Jr, McCormick WF, Zellweger H. Type IV glycogenosis (amylopectinosis): Light and electron microscopic observations. Arch Pathol 1970;90:354-63. 3. Servidei S, Riepe RE, Langston C , et al. Severe cardiopathy in branching enzyme deficiency. J Pediatr 1987; 11151-6. 4. Yokota T, Ishihara T, Kawano H , et al. Immunological homogeneity of Lafora body, corpora amylacea, basophilic degeneration in heart, and intracytoplasmic inclusions of liver and heart in type IV glycogenesis. Acta Pathol Jpn 1987;37:941-6.
5. Lowe J , Blanchard A, Morrell K, et al. Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson’s disease, Pick’s disease, and Alzheimer’s disease as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and Mallory bodies in alcoholic liver disease. J Pathol 1988;155:9-15. 6. Brown BI, Brown D H . Lack of an a1,4 glucan: a1,4 glucan 6 glycosyl transferase in a case of type IV glycogenesis. Proc Natl Acad Sci USA 1966;56:725-9.
ISSN: 0277-0938 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ipdp17
Leukocyte Inclusions in Glycogen Storage Disease, Type IV To cite this article: (1992) Leukocyte Inclusions in Glycogen Storage Disease, Type IV, Pediatric Pathology, 12:6, 903-905, DOI: 10.3109/15513819209024249 To link to this article: http://dx.doi.org/10.3109/15513819209024249
Published online: 09 Jul 2009.
Submit your article to this journal
Article views: 5
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipdp17 Download by: [69.162.139.9]
Date: 30 March 2016, At: 05:12
LETTER TO THE EDITOR
Downloaded by [69.162.139.9] at 05:12 30 March 2016
LEUKOCYTE INCLUSIONS IN GLYCOGEN STORAGE DISEASE. TYPE IV The existence of some metabolic disorders, including glycogen storage disease type 11, can be adduced from careful examination of the peripheral blood film in the form of vacuoles or inclusions in the leukocytes. We wish to record the observation of periodic acid-Schiff (PAS)-positive, diastase-resistant inclusions in the neutrophils and lymphocytes of a patient who had glycogen storage disease type IV, a condition that is not included in the lists of morphologic clues to be found in the blood (1). Glycogen storage disease type IV (Andersen disease, McKusick, 23250), a deficiency of the branching enzyme, results in the intracellular deposition of a relatively insoluble amylopectin-like material, seen in many organs but most prominently in liver, heart, muscle, central nervous system, and skin (2, 3). The intracytoplasmic inclusions stain with PAS and resist diastase digestion but are vulnerable to pectinase digestion (2). The inclusions characteristically stain with colloidal iron and are said to be variably blue to purple-brown when reacted with iodine (2). The inclusions are antigenically similar to Lafora bodies (4), suggesting that they are ubiquitinated (5). Although the enzyme defect is readily detectable in leukocytes ( 6 ) , illustrations of leukocyte inclusions are not recorded.. A 32-month-old boy underwent liver transplantation for cirrhosis caused by enzymatically confirmed glycogen storage disease type IV. The liver contained the characteristic inclusions in the hepatocytes. Portal macrophages and macrophages in a hilar lymph node contained complex ceroid (lipochrome) that had very similar tinctorial properties to the hepatocellular inclusions, suggesting that the ingested material was derived from the inclusions. No abnormality was detected, even in retrospect, on the Wright-Giemsastained peripheral blood smear; however, when the blood films made from EDTA-collected blood samples were stained with PAS, multiple angular inclusions of varying shape and size were seen in 16% of the neutrophils. These irregular cytoplasmic inclusions, like those elsewhere in the body, resisted digestion by diastase (Fig. 1A). The inclusions gave a dark brown color when treated with Lugol’s iodine (Fig. lB), indicating their similarity to the somatic inclusions (2). A rare lymphocyte had more regularly distributed and round PASpositive, diastase-resistant globules (Fig. 1C). Electron microscopy using standard techniques on a glutaraldehyde-fixed buffy coat revealed a lymphocyte with a large, round membrane-bound cytoplasmic inclusion containing short, occasionally branched, randomly oriented fdaments (Fig. 2). The filaments measured 6-8 nm in diameter, characteristic Pediatric Patholoo, 12:903-905, 1992 Copyright @ 1992 by Hemisphere Publishing Corporation
903
Downloaded by [69.162.139.9] at 05:12 30 March 2016
904
LETTER TO THE EDITOR
of the amylopectin-like material found in glycogen storage disease type IV. A number of neutrophils contained mottled, medium dense, membrane-bound cytoplasmic masses of amorphous material resembling ceroid but without the characteristic filamentous structure of the amylopectin-like material. Cytoplasmic inclusions with characteristic staining qualities can be found in the neutrophils and lymphocytes in glycogen storage disease type IV. Whereas the lymphocyte inclusions are typical and resemble those found in other organs by ultrastructural study, the more obvious neutrophil inclusions may represent altered and phagocytosed material derived from the amylopectin-like inclusions similar to that found in hepatic portal and hilar lymph node macrophages. Fibroblasts from the patient and lymphocytes from his parents were banked at the NIGMS Cell Repository, Cornell Institute for Medical Research, Camden, NJ (GM12131, patient; GM12136, mother; GM12137, father).
Lila Penchansky, MD Rocco M. Agostini, BS Ronald Jaffe, MD Department o f Pathology, University o f Pittsburgh and Children 5 Hospital o f Pittsburgh Main Tower Rm. 5938 Pittsburgh, Pennsylvania 15213 Address reprint requests to first author at address above.
FIGURE 1. Peripheral blood smear from a patient with glycogen storage disease, type IV. X 1000. (A) A neutrophil contains irregular clumps of PAS-positive material that resists diastase digestion. (B) When reacted with Lugol's iodine the cytoplasmic inclusions give a brown color. Though not specific, the reaction is characteristic. (C) A lymphocyte has a ring of PAS-positive, diastase-resistant granules in the cytoplasm.
Downloaded by [69.162.139.9] at 05:12 30 March 2016
LETTER TO THE EDITOR
905
FIGURE 2. (A) A lymphocyte has a large, rounded, membrane-bound inclusion (arrow). Uranyl acetatelead citrate, X 19,500. (B) A higher-power image of the inclusion reveals short, occasionally branched, 6-8nm filaments consistent with the amylopectin-like material of glycogenosis IV. Uranyl acetate-lead citrate, x91,ooo.
REFERENCES 1. Kolodny EH, Boustany R M . Storage diseases of the reticuloendothelial system. In: Nathan DG, Oski FA, eds. Hematology of Infancy and Childhood. 3rd ed. Philadelphia, W. B. Saunders, 1987;1217. 2. Schochet SS Jr, McCormick WF, Zellweger H. Type IV glycogenosis (amylopectinosis): Light and electron microscopic observations. Arch Pathol 1970;90:354-63. 3. Servidei S, Riepe RE, Langston C , et al. Severe cardiopathy in branching enzyme deficiency. J Pediatr 1987; 11151-6. 4. Yokota T, Ishihara T, Kawano H , et al. Immunological homogeneity of Lafora body, corpora amylacea, basophilic degeneration in heart, and intracytoplasmic inclusions of liver and heart in type IV glycogenesis. Acta Pathol Jpn 1987;37:941-6.
5. Lowe J , Blanchard A, Morrell K, et al. Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson’s disease, Pick’s disease, and Alzheimer’s disease as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and Mallory bodies in alcoholic liver disease. J Pathol 1988;155:9-15. 6. Brown BI, Brown D H . Lack of an a1,4 glucan: a1,4 glucan 6 glycosyl transferase in a case of type IV glycogenesis. Proc Natl Acad Sci USA 1966;56:725-9.
