- Email: [email protected]
Bone marrow in the Batten-Vogt syndrome
Journal of the neurolo#ical Sciences, 1975, 25:197-203 :~ Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
197
Bone Marrow in the Batten-Vogt Syndrome N. G A D O T H * , P. O'CROININ AND I. J. BUTLER Departments of Neuroloqy and Pediatric Hematoloqy, The Johns Hopkins Hospital, Baltimore, Md. ( U.S.A. ) {Received 19 November, 1974}
I NTRODUCTION
Ceroid-lipofuscinosis (Batten-Vogt syndrome) is the name now utilized for a progressive degenerative disease of the central nervous system in children. Previously termed Spielmeyer-Vogt, Jansky-Bielchowsky, or Batten's disease, it is characterized clinically by psychomotor deterioration, seizures and progressive loss of visual function. Pathologically there is accumulation of a non-ganglioside, ceroid-lipofuscin material in neurons and extraneuronal organs (Sj6vall and Ericsson 1933 ; Kristensson, Rayner and Sourander 1965 ; Kristensson and Sourander 1966 ; Perboll 1967 ; Dayan and Trickey 1970; Witzleblen, Smith, Nelson, Monteleone and Livingston 1971; Carpenter, Karpati and Andermann 1972; Van Haelst and Gabre~ls 1972; Joosten, Gabre~ls, Stadhouders, Bolmers and Gabre~ls-Festen 1973). Diagnosis at present depends on the demonstration of ceroid-lipofuscin in brain and various organs by special staining and autofluorescent techniques. In 1950, Wewalka described the sea-blue nature of macrophages in bone marrow from a patient with splenomegaly and abnormal retinal maculae (Wewalka 1950). Following the demonstration of sea-blue histiocytes in other organs of patients with hepatosplenomegaly and hypersplenism, the syndrome became known as primary sea-blue histiocytosis. In addition to the characteristic sea-blue appearance using Wright or Giemsa stain, material stored in these cells shares the histochemical properties of ceroid, having a positive reaction to periodic acid-Schiff (before and after diastase digestion), Oil red 0 and Sudan B black stains, and shows bright yellow autofluorescence under ultraviolet light (Rywlin, Hernandez, Chastain and Pardo 1971 ; Silverstein and Ellefson 1972: Sawitsky, Rosner and Chadsky 1972). The purpose of this report is to show the value of bone marrow examination in screening patients with ceroid-lipofuscinosis. Kristensson found ceroid-like material in large reticuloendothelial cells from bone marrow of patients with Batten-Vogt The research was supported in part by Hematology Training Grant No. 5T01-AM05260-13 and funds from the John A. Hartford Foundation Inc., and by USPHS grant No. NS-08719. * Reprint requests to : N. Gadoth, M.D., Department of Neurology, The Johns Hopkins Hospital, 601 N. Broadway, Baltimore, Md. 21205, U.S.A.
198
N. G A I ) O T H , I'. O ' ( ' R O I N I N , I. J. BUI'I,ER
syndrome, but without staining by Wright or Giemsa stains the sea-blue nature ol
these cells was not shown (Kristensson et al. 1965). Bone marrows were examined in 6 patients with Batten-Vogt syndrome. In all cases autofluorescent material was seen and in 5 sea-blue histiocytes were demonstrated. C L I N I C A L HISTORIES
Clinical and diagnostic features of the patients with the Batten-Vogt syndrome are summarized in Table 1. All were Caucasian, and non-Jewish in origin. Seizures, mental deterioration and progressive loss of visual function were the major clinical manifestations in all patients. The fundoscopic appearance and abnormalities of the electroretinogram (ERG) and electroencephalogram (EEG) were consistent with the accepted diagnostic criteria of the Batten-Vogt syndrome (Zeman, Donahue, Dyken and Green 1970). The known neuronal storage diseases of the central nervous system (TayTABLE 1 BATTEN
V O G T S Y N D R O M E - - C I . I N I C A I , A N D I N V E S T I ( i A T 1 V E F I N D I N G S IN 6 CASES
Case No. (as(_, No.
1
2
3
4
5
6
Sex
M
M
M
M
F
M
Siblings affected
Ia
Ia
Age of onset (yr)
5
5
1
9
1.5
3
Mental deterioration
+
+
+
+
+
+
Seizures a n d a b n o r m a l EEG
+
+
+
+
+
+
Visual failure
+
+
+
+
+
+
Optic fundus
c
c
c
c
1
slight macular
abnormality
pigmentation Abnormal ERG
+
+
+
+
N.D. b
+
Diagnostic brain b i o p s y
+
N.D.
N.D.
+
+
+
Sea-blue histiocytes in b o n e m a r r o w
+
_
+
Autofluorescence in b o n e m a r r o w
++
+
+
"Siblings. b N . D . = N o t done. ¢ O p t i c atrophy, a t t e n u a t e d vessels.
++
+
+
BONE MARROW IN THE BATTEN-VOGT SYNDROME
199
Sachs disease, metachromatic leucodystrophy and various gangliosidoses) were excluded by the appropriate metabolic studies and there was no evidence of foamy histiocytes in the marrow such as are seen in Gaucher's or Niemann-Pick disease. The basis for diagnosis in Case 2 (a brother of Case 1) and Case 3, was the typical clinical picture. A brain biopsy confirmed the diagnosis in Cases 1, 4, 5, and 6. In 2 families there was another affected sibling and from 1 of these (a brother of Case 4) the brain biopsy was also confirmatory. According to the age of onset and clinical picture, these patients can be separated into the infantile form of Jansky-Bielschowsky (Cases 3 and 5) and the more common juvenile form of Spielmeyer-Vogt (Cases 1, 2, 3, and 6). At present both types are considered under the Batten-Vogt syndrome (Zeman et al. 1970). MATERIAL AND METHODS
Autofluorescent material in bone marrow smears was demonstrated under ultraviolet light (HBO 200 mercury lamp, BG 1z and K530 primary and secondary filters), and the sea-blue nature of cells by the Wright stain. Six patients with Batten-Vogt syndrome were studied by these methods. A control group of 5 children and 3 adults was similarly studied for a variety of hematological and other non-neurological conditions, including drug-induced neutropenia, multiple congenital anomalies, iron deficiency anemia, hepatosplenomegaly, cervical lymph node enlargement and increased plasma cell count in peripheral blood. Bone marrow smears from Cases 1 and 2 were stained by periodic acid-Schiff (before and after diastase digestion), Oil red 0, Sudan B black and acid-fast techniques. Thin, deparaffined sections of brain from Cases 1 and 4 were examined for autofluorescence. In addition, brain tissue from Cases 1, 4, 5, and 6 were examined using routine histochemical methods and light microscopy and by electron microscopy in Cases 1 and 4. RESULTS
Neither sea-blue histiocytes nor abnormal autofluorescence was demonstrated in the control bone marrows. In 5 of the 6 cases with the Batten-Vogt syndrome, scattered sea-blue histiocytes were seen on careful examination in marrow smears (Fig. 1). Cells from Cases 1 and 2 stained positive to periodic acid-Schiff (before and after diastase), Oil red 0, Sudan B black, and slightly positive to the acid-fast technique. Yellow autofluorescence was seen in the bone marrow of all 6 patients. The large, autofluorescent cells, containing bright yellow granular material, were easily identified (Fig. 2). The amount of storage material in cells was variable with some being full and swollen, while other cells showed a small amount of granular, autofluorescent material and some only 1 or 2 granules per cell (Fig. 3). In Cases 1 and 4, unstained brain tissue was available for adequate autofluorescent study and the amount of material stored in brain could be compared to that in the marrow. Sea-blue histiocytes were easily seen in Case 1, neuronal storage was marked, as was autofluorescence in marrow and brain tissue. In Case 4, the fewer sea-blue histiocytes and autofluorescent cells seen in marrow correlated with the scanty storage and autofluorescence in the nervous tissue.
200
N. ( i A I ) ( ) T I I , I'. O ' C R ( ) I N I N . 1. ,1. I~lJI It!R
l-ig. I. Sea-blue histioc'~,te from b o n e m a r r o w of Case 1, W r i g h t stain, ~< 45(.
Fig. 2. A u t o f l u o r e s c e n t cells from b o n e m a r r o w of Case 1. × 125.
BONE MARROW IN THE BATTEN--VOGT SYNDROME
201
Fig. 3. Granular appearance of autofluorescent cell from bone marrow of Case 2. x 125. DI SC USSION
In 6 patients with the clinical features of Batten-Vogt syndrome, careful examination of bone marrow showed maximum autofluorescence in cells at a wavelength of 530 nm. Hyd6n and Lindstrom reported that the maximal fluorescence for lipofuscin in nerve cells is in the 440~60 nm and 530-560 nm regions (Hyd~n and Lindstrom 1950). The presence of sea-blue histiocytes in bone marrow from 5 of the 6 patients was intriguing in view of the shared histochemical properties of the material stored in these cells and ceroid-lipofuscin (Rywlin et al. 1971). The amount of accumulated material in brain correlated with that in bone marrow in the 2 cases (Cases 1 and 4) where adequate material was available for comparison. Sea-blue histiocytosis can occur as a primary, hereditary form, in which large numbers of cells are seen, or as a secondary acquired condition with fewer sea-blue histiocytes in bone marrow. Among the variety of diseases with a secondary sea-blue histiocytosis are hematological disorders with an increased cell turnover (leukemia, idiopathic thrombocytopenic purpura, sickle cell anemia), lipid storage diseases (Niemann-Pick, Tay-Sachs and Wolman's disease), and hyperlipoproteinemia (Sawitsky et al. 1972). Ceroid-lipofuscin is thought to be the auto-oxidative product of polyunsaturated fatty acids and in addition, these fatty acids appear necessary for experimental in vivo and in vitro ceroid-like substance formation. Red blood cells and necrotic tissue, in
202
N. GAI)OTH, P. O'CR()ININ, I. J. BUTI.ER
the presence of polyunsaturated fatty acids, hasten the production of the ceroid-like material, probably by acting as a surface for deposition of the newly formed pigment (Casselman 1951). In those hematological conditions with a rapid turnover of ceils, an increased polyunsaturated fatty acid production could result in ceroid-lipofuscin and their subsequent ingestion by macrophages in bone marrow could explain the presence of sea-blue histiocytes. The neuronal storage of ceroid-lipfuscin in the Batten-Vogt syndrome may not be explained by phagocytosis, but could result from intracellular conversion of polyunsaturated fatty acid to ceroid-lipofuscin. Involvement of viscera in patients with ceroid lipofuscinosis syndrome may be attributed to a diffuse abnormality in detoxification of lipid peroxides formed in polyunsaturated fatty acid metabolism. A deficiency in peroxidase has been reported in leucocytes and thyroid from patients with neuronal lipofuscinosis (Armstrong, Dimmitt and Van Wormer 1974). In patients with a clinical history and physical findings which suggest Batten-Vogt syndrome, in whom known causes of neuronal storage disease have been excluded, bone marrow examination for sea-blue histiocytes and cells with autofluorescent material offers a useful screening method for ceroid-lipofuscinosis. SUMMARY
Six children with clinical and pathological features of Batten-Vogt syndrome showed autofluorescent material in bone marrow cells and in 5 of them sea-blue histiocytes were seen. It is suggested that bone marrow examination for sea-blue histiocytes and autofluorescence is a useful screening test for ceroid-lipofuscinosis.
REFERENCES ARMSTRONG, D., S. DIMMIT AND D. E. VAN WORMER (1974) Studies in Batten's disease, Part I (Peroxidase deficiency in granulocytes), Arch. Neurol. (Chic.), 30: 144-152. CARPENTER, S., G. KARPATI AND F. ANDERMAN (1972) Specific involvement of muscle, nerve and skin in late infantile and juvenile amaurotic idiocy, Neurotoqv (Minneap.), 22 : 170-t 86. CASSELMAN,W. G. B. (1951 ) The in vitro preparation and histochemical properties of substances resembling ceroid, J. exp. Med., 94: 549-562. DAYAN, A. D, AND R. J. TRICKEY (1970) Thryoid involvement in juvenile amaurotic idiocy (Batten's disease), Lancet, 2: 296-297. HYDI~N, H. AND B. LINDSTROM (1950j Microspectrographic studies on the yellow pigment in nerve cells, Discuss. Faraday Sot., 9: 436-441. JOOSTEN,E., F. GABREELS, A. STAI)HOtII)I~RS. D. BOLMERSAND A. GABRE~t.s-FESTEN (1973) Involvement of sural nerve in neuronal ceroid-lipofuseinosis - - Report of two cases, Neuropdidiatrie, 4: 98-I 10. K RISTENSSON, K. AND P. SOURANDER (1966) Occurrence of lipofuscin in inherited metabolic disorders affecting the nervous system. J. Neurol. Neurosurg. P.~vchiat., 29 : 113-118. KRISTENSSON, K., S. RAYNER AND P. SOURANDER(1965) Visceral involvement in juvenile amaurotic idiocy, Acta neuropath. ( Berl. ), 4: 421-424, PERBeLL, O. (1967) Vascular and pineal body involvement in juvenile amaurotic idiocy (Batten's disease/, Acta neuropath. (Bed.), 8: 210-214. RYWLIN, A. M., J. A. HERNANDEZ, D. E. CHASTAIN AND V. PARDO (1971) Ceroid histiocytosis of spleen and bone marrow in idiopathic thrombocytopenic purpura (ITP) - A contribution to the understanding of the sea-blue histiocyte, Blood, 37: 587-593. SAWITSKY,A., F. ROSNE~RAND S. CFIADSKY(1972} The sea-blue histiocyte syndromel A Review - Genetic and biochemical studies, Sere. Hernat., 9: 285-297.
BONE MARROW IN THE BATTEN-VOGT SYNDROME
203
SILVERSTEIN, M. N. AND R. D. ELLEFSON (1972) The syndrome of the sea-blue histiocyte, Sere. Hemat., 9 : 299-307. SJ()VALL, E. AND E. ERICSSON (1933) The anatomical type in the Swedish cases of juvenile amaurotic idiocy, Acta path. microbiol, scand., 16 (Suppl.): 460-471. VAN HAELST. U. J. G. M. AND F. J. M. GABREi~LS(1972). The electron microscopic study o f the appendix as early diagnostic means in Batten-Spielmeyer-Vogt disease, A cta neuropath. (Berl.), 21:169 175. WEWALKA. F. (1950) Zur Frage der "blauen Pigmentmakrophagen" in Sternalpunktat, Wie,. /,litl. W~chr., 62:788 791. WITZLEBLEN, C. N., K. SMITH, J. S. NELSON. P. L. MONFIiLI!ONI!AND D. LIVINGSTON(1971) Ultrastructural studies in late-onset amaurotic idiocy - Lymphocyte inclusion as a diagnostic marker, J. Pediat., 79: 285-293. ZEMAN,W., S. DONAHUE,P. DVKEN AND J. GREEN (1970) The neuronal ceroid-lipofuscinoses (Batten Vogt syndrome). In: P. J. VINXCErqXrCDG. W. BRUVN(Eds.), Handbook ofClinicalNeurolooy, Vol. 10 (Leucodystrophies and Poliodystrophies), North-Holland Publishing Company, Amsterdam, pp. 588-679.
197
Bone Marrow in the Batten-Vogt Syndrome N. G A D O T H * , P. O'CROININ AND I. J. BUTLER Departments of Neuroloqy and Pediatric Hematoloqy, The Johns Hopkins Hospital, Baltimore, Md. ( U.S.A. ) {Received 19 November, 1974}
I NTRODUCTION
Ceroid-lipofuscinosis (Batten-Vogt syndrome) is the name now utilized for a progressive degenerative disease of the central nervous system in children. Previously termed Spielmeyer-Vogt, Jansky-Bielchowsky, or Batten's disease, it is characterized clinically by psychomotor deterioration, seizures and progressive loss of visual function. Pathologically there is accumulation of a non-ganglioside, ceroid-lipofuscin material in neurons and extraneuronal organs (Sj6vall and Ericsson 1933 ; Kristensson, Rayner and Sourander 1965 ; Kristensson and Sourander 1966 ; Perboll 1967 ; Dayan and Trickey 1970; Witzleblen, Smith, Nelson, Monteleone and Livingston 1971; Carpenter, Karpati and Andermann 1972; Van Haelst and Gabre~ls 1972; Joosten, Gabre~ls, Stadhouders, Bolmers and Gabre~ls-Festen 1973). Diagnosis at present depends on the demonstration of ceroid-lipofuscin in brain and various organs by special staining and autofluorescent techniques. In 1950, Wewalka described the sea-blue nature of macrophages in bone marrow from a patient with splenomegaly and abnormal retinal maculae (Wewalka 1950). Following the demonstration of sea-blue histiocytes in other organs of patients with hepatosplenomegaly and hypersplenism, the syndrome became known as primary sea-blue histiocytosis. In addition to the characteristic sea-blue appearance using Wright or Giemsa stain, material stored in these cells shares the histochemical properties of ceroid, having a positive reaction to periodic acid-Schiff (before and after diastase digestion), Oil red 0 and Sudan B black stains, and shows bright yellow autofluorescence under ultraviolet light (Rywlin, Hernandez, Chastain and Pardo 1971 ; Silverstein and Ellefson 1972: Sawitsky, Rosner and Chadsky 1972). The purpose of this report is to show the value of bone marrow examination in screening patients with ceroid-lipofuscinosis. Kristensson found ceroid-like material in large reticuloendothelial cells from bone marrow of patients with Batten-Vogt The research was supported in part by Hematology Training Grant No. 5T01-AM05260-13 and funds from the John A. Hartford Foundation Inc., and by USPHS grant No. NS-08719. * Reprint requests to : N. Gadoth, M.D., Department of Neurology, The Johns Hopkins Hospital, 601 N. Broadway, Baltimore, Md. 21205, U.S.A.
198
N. G A I ) O T H , I'. O ' ( ' R O I N I N , I. J. BUI'I,ER
syndrome, but without staining by Wright or Giemsa stains the sea-blue nature ol
these cells was not shown (Kristensson et al. 1965). Bone marrows were examined in 6 patients with Batten-Vogt syndrome. In all cases autofluorescent material was seen and in 5 sea-blue histiocytes were demonstrated. C L I N I C A L HISTORIES
Clinical and diagnostic features of the patients with the Batten-Vogt syndrome are summarized in Table 1. All were Caucasian, and non-Jewish in origin. Seizures, mental deterioration and progressive loss of visual function were the major clinical manifestations in all patients. The fundoscopic appearance and abnormalities of the electroretinogram (ERG) and electroencephalogram (EEG) were consistent with the accepted diagnostic criteria of the Batten-Vogt syndrome (Zeman, Donahue, Dyken and Green 1970). The known neuronal storage diseases of the central nervous system (TayTABLE 1 BATTEN
V O G T S Y N D R O M E - - C I . I N I C A I , A N D I N V E S T I ( i A T 1 V E F I N D I N G S IN 6 CASES
Case No. (as(_, No.
1
2
3
4
5
6
Sex
M
M
M
M
F
M
Siblings affected
Ia
Ia
Age of onset (yr)
5
5
1
9
1.5
3
Mental deterioration
+
+
+
+
+
+
Seizures a n d a b n o r m a l EEG
+
+
+
+
+
+
Visual failure
+
+
+
+
+
+
Optic fundus
c
c
c
c
1
slight macular
abnormality
pigmentation Abnormal ERG
+
+
+
+
N.D. b
+
Diagnostic brain b i o p s y
+
N.D.
N.D.
+
+
+
Sea-blue histiocytes in b o n e m a r r o w
+
_
+
Autofluorescence in b o n e m a r r o w
++
+
+
"Siblings. b N . D . = N o t done. ¢ O p t i c atrophy, a t t e n u a t e d vessels.
++
+
+
BONE MARROW IN THE BATTEN-VOGT SYNDROME
199
Sachs disease, metachromatic leucodystrophy and various gangliosidoses) were excluded by the appropriate metabolic studies and there was no evidence of foamy histiocytes in the marrow such as are seen in Gaucher's or Niemann-Pick disease. The basis for diagnosis in Case 2 (a brother of Case 1) and Case 3, was the typical clinical picture. A brain biopsy confirmed the diagnosis in Cases 1, 4, 5, and 6. In 2 families there was another affected sibling and from 1 of these (a brother of Case 4) the brain biopsy was also confirmatory. According to the age of onset and clinical picture, these patients can be separated into the infantile form of Jansky-Bielschowsky (Cases 3 and 5) and the more common juvenile form of Spielmeyer-Vogt (Cases 1, 2, 3, and 6). At present both types are considered under the Batten-Vogt syndrome (Zeman et al. 1970). MATERIAL AND METHODS
Autofluorescent material in bone marrow smears was demonstrated under ultraviolet light (HBO 200 mercury lamp, BG 1z and K530 primary and secondary filters), and the sea-blue nature of cells by the Wright stain. Six patients with Batten-Vogt syndrome were studied by these methods. A control group of 5 children and 3 adults was similarly studied for a variety of hematological and other non-neurological conditions, including drug-induced neutropenia, multiple congenital anomalies, iron deficiency anemia, hepatosplenomegaly, cervical lymph node enlargement and increased plasma cell count in peripheral blood. Bone marrow smears from Cases 1 and 2 were stained by periodic acid-Schiff (before and after diastase digestion), Oil red 0, Sudan B black and acid-fast techniques. Thin, deparaffined sections of brain from Cases 1 and 4 were examined for autofluorescence. In addition, brain tissue from Cases 1, 4, 5, and 6 were examined using routine histochemical methods and light microscopy and by electron microscopy in Cases 1 and 4. RESULTS
Neither sea-blue histiocytes nor abnormal autofluorescence was demonstrated in the control bone marrows. In 5 of the 6 cases with the Batten-Vogt syndrome, scattered sea-blue histiocytes were seen on careful examination in marrow smears (Fig. 1). Cells from Cases 1 and 2 stained positive to periodic acid-Schiff (before and after diastase), Oil red 0, Sudan B black, and slightly positive to the acid-fast technique. Yellow autofluorescence was seen in the bone marrow of all 6 patients. The large, autofluorescent cells, containing bright yellow granular material, were easily identified (Fig. 2). The amount of storage material in cells was variable with some being full and swollen, while other cells showed a small amount of granular, autofluorescent material and some only 1 or 2 granules per cell (Fig. 3). In Cases 1 and 4, unstained brain tissue was available for adequate autofluorescent study and the amount of material stored in brain could be compared to that in the marrow. Sea-blue histiocytes were easily seen in Case 1, neuronal storage was marked, as was autofluorescence in marrow and brain tissue. In Case 4, the fewer sea-blue histiocytes and autofluorescent cells seen in marrow correlated with the scanty storage and autofluorescence in the nervous tissue.
200
N. ( i A I ) ( ) T I I , I'. O ' C R ( ) I N I N . 1. ,1. I~lJI It!R
l-ig. I. Sea-blue histioc'~,te from b o n e m a r r o w of Case 1, W r i g h t stain, ~< 45(.
Fig. 2. A u t o f l u o r e s c e n t cells from b o n e m a r r o w of Case 1. × 125.
BONE MARROW IN THE BATTEN--VOGT SYNDROME
201
Fig. 3. Granular appearance of autofluorescent cell from bone marrow of Case 2. x 125. DI SC USSION
In 6 patients with the clinical features of Batten-Vogt syndrome, careful examination of bone marrow showed maximum autofluorescence in cells at a wavelength of 530 nm. Hyd6n and Lindstrom reported that the maximal fluorescence for lipofuscin in nerve cells is in the 440~60 nm and 530-560 nm regions (Hyd~n and Lindstrom 1950). The presence of sea-blue histiocytes in bone marrow from 5 of the 6 patients was intriguing in view of the shared histochemical properties of the material stored in these cells and ceroid-lipofuscin (Rywlin et al. 1971). The amount of accumulated material in brain correlated with that in bone marrow in the 2 cases (Cases 1 and 4) where adequate material was available for comparison. Sea-blue histiocytosis can occur as a primary, hereditary form, in which large numbers of cells are seen, or as a secondary acquired condition with fewer sea-blue histiocytes in bone marrow. Among the variety of diseases with a secondary sea-blue histiocytosis are hematological disorders with an increased cell turnover (leukemia, idiopathic thrombocytopenic purpura, sickle cell anemia), lipid storage diseases (Niemann-Pick, Tay-Sachs and Wolman's disease), and hyperlipoproteinemia (Sawitsky et al. 1972). Ceroid-lipofuscin is thought to be the auto-oxidative product of polyunsaturated fatty acids and in addition, these fatty acids appear necessary for experimental in vivo and in vitro ceroid-like substance formation. Red blood cells and necrotic tissue, in
202
N. GAI)OTH, P. O'CR()ININ, I. J. BUTI.ER
the presence of polyunsaturated fatty acids, hasten the production of the ceroid-like material, probably by acting as a surface for deposition of the newly formed pigment (Casselman 1951). In those hematological conditions with a rapid turnover of ceils, an increased polyunsaturated fatty acid production could result in ceroid-lipofuscin and their subsequent ingestion by macrophages in bone marrow could explain the presence of sea-blue histiocytes. The neuronal storage of ceroid-lipfuscin in the Batten-Vogt syndrome may not be explained by phagocytosis, but could result from intracellular conversion of polyunsaturated fatty acid to ceroid-lipofuscin. Involvement of viscera in patients with ceroid lipofuscinosis syndrome may be attributed to a diffuse abnormality in detoxification of lipid peroxides formed in polyunsaturated fatty acid metabolism. A deficiency in peroxidase has been reported in leucocytes and thyroid from patients with neuronal lipofuscinosis (Armstrong, Dimmitt and Van Wormer 1974). In patients with a clinical history and physical findings which suggest Batten-Vogt syndrome, in whom known causes of neuronal storage disease have been excluded, bone marrow examination for sea-blue histiocytes and cells with autofluorescent material offers a useful screening method for ceroid-lipofuscinosis. SUMMARY
Six children with clinical and pathological features of Batten-Vogt syndrome showed autofluorescent material in bone marrow cells and in 5 of them sea-blue histiocytes were seen. It is suggested that bone marrow examination for sea-blue histiocytes and autofluorescence is a useful screening test for ceroid-lipofuscinosis.
REFERENCES ARMSTRONG, D., S. DIMMIT AND D. E. VAN WORMER (1974) Studies in Batten's disease, Part I (Peroxidase deficiency in granulocytes), Arch. Neurol. (Chic.), 30: 144-152. CARPENTER, S., G. KARPATI AND F. ANDERMAN (1972) Specific involvement of muscle, nerve and skin in late infantile and juvenile amaurotic idiocy, Neurotoqv (Minneap.), 22 : 170-t 86. CASSELMAN,W. G. B. (1951 ) The in vitro preparation and histochemical properties of substances resembling ceroid, J. exp. Med., 94: 549-562. DAYAN, A. D, AND R. J. TRICKEY (1970) Thryoid involvement in juvenile amaurotic idiocy (Batten's disease), Lancet, 2: 296-297. HYDI~N, H. AND B. LINDSTROM (1950j Microspectrographic studies on the yellow pigment in nerve cells, Discuss. Faraday Sot., 9: 436-441. JOOSTEN,E., F. GABREELS, A. STAI)HOtII)I~RS. D. BOLMERSAND A. GABRE~t.s-FESTEN (1973) Involvement of sural nerve in neuronal ceroid-lipofuseinosis - - Report of two cases, Neuropdidiatrie, 4: 98-I 10. K RISTENSSON, K. AND P. SOURANDER (1966) Occurrence of lipofuscin in inherited metabolic disorders affecting the nervous system. J. Neurol. Neurosurg. P.~vchiat., 29 : 113-118. KRISTENSSON, K., S. RAYNER AND P. SOURANDER(1965) Visceral involvement in juvenile amaurotic idiocy, Acta neuropath. ( Berl. ), 4: 421-424, PERBeLL, O. (1967) Vascular and pineal body involvement in juvenile amaurotic idiocy (Batten's disease/, Acta neuropath. (Bed.), 8: 210-214. RYWLIN, A. M., J. A. HERNANDEZ, D. E. CHASTAIN AND V. PARDO (1971) Ceroid histiocytosis of spleen and bone marrow in idiopathic thrombocytopenic purpura (ITP) - A contribution to the understanding of the sea-blue histiocyte, Blood, 37: 587-593. SAWITSKY,A., F. ROSNE~RAND S. CFIADSKY(1972} The sea-blue histiocyte syndromel A Review - Genetic and biochemical studies, Sere. Hernat., 9: 285-297.
BONE MARROW IN THE BATTEN-VOGT SYNDROME
203
SILVERSTEIN, M. N. AND R. D. ELLEFSON (1972) The syndrome of the sea-blue histiocyte, Sere. Hemat., 9 : 299-307. SJ()VALL, E. AND E. ERICSSON (1933) The anatomical type in the Swedish cases of juvenile amaurotic idiocy, Acta path. microbiol, scand., 16 (Suppl.): 460-471. VAN HAELST. U. J. G. M. AND F. J. M. GABREi~LS(1972). The electron microscopic study o f the appendix as early diagnostic means in Batten-Spielmeyer-Vogt disease, A cta neuropath. (Berl.), 21:169 175. WEWALKA. F. (1950) Zur Frage der "blauen Pigmentmakrophagen" in Sternalpunktat, Wie,. /,litl. W~chr., 62:788 791. WITZLEBLEN, C. N., K. SMITH, J. S. NELSON. P. L. MONFIiLI!ONI!AND D. LIVINGSTON(1971) Ultrastructural studies in late-onset amaurotic idiocy - Lymphocyte inclusion as a diagnostic marker, J. Pediat., 79: 285-293. ZEMAN,W., S. DONAHUE,P. DVKEN AND J. GREEN (1970) The neuronal ceroid-lipofuscinoses (Batten Vogt syndrome). In: P. J. VINXCErqXrCDG. W. BRUVN(Eds.), Handbook ofClinicalNeurolooy, Vol. 10 (Leucodystrophies and Poliodystrophies), North-Holland Publishing Company, Amsterdam, pp. 588-679.