Neuronal ceroid-lipofuscinosis, a type of amaurotic family idiocy: clinical and pathological study of four cases

Queiroz, Luciano de Souza; Cruz Neto, Joaquim N. da; Faria, J. Lopes de

doi:10.1590/S0004-282X1974000100001

Abstracts

Neuronal ceroid-lipofuscinosis (NCL) is a recent term, proposed for acurate designation of the late-onset types of Amaurotic Family Idiocy (AFI). Histopathology shows ubiquitous intraneuronal accumulation of lipopigments, being the most important factor for characterization of the entity at present time. Biochemical changes and pathogenesis are obscure. NCL is in contrast to the infantile type of AFI (Tay-Sachs disease), in which intraneuronal accumulation of gangliosides (sphingolipids) is due to the well known deficiency of a lysosomal enzyme. The authors report on four cases of NCL, two brothers of the late infantile (Jansky-Bielschowsky) type and a brother and a sister of the juvenile (Spielmeyer-Sjögren) type. One autopsy and three cortical biopsies revealed moderate to severe distention of the neurons by lipopigment, with nerve cell loss, gliosis and cerebral atrophy. Lipopigment was also increased in liver, heart and spleen. The patients were the first in Brazilian literature in whom the storage material was identified as lipopigment by histochemical methods. A brief summary of the clinical features of NCL is presented, and relevant problems are discussed, concerning interpretation of the nature of the storage material, and significance of the disease for gerontological research.

Estudos histoquímicos, bioquímicos e ultraestruturais permitiram recentemente distinguir dois tipos de entidades nosológicas dentre as doenças conhecidas como "Idiotia amaurótica familiar" (IAF). O primeiro, que inclue a doença de Tay-Sachs, ou tipo infantil de IAF, é constituido por doenças de armazenamento de gangliósides. Sua patogenia é conhecida, baseando-se em deficiências de enzimas lisossômicos. O segundo grupo, cuja patogenia é desconhecida, foi recentemente designado "Ceróide-lipofuscinose neuronal" (CLN) por Zeman e colaboradores. Corresponde aos tipos infantil tardio, juvenil e adulto de IAF, caracterizando-se histopatologicamente pelo acúmulo intraneuronal de lipopigmentos. Os autores descrevem quatro casos de Ceróide-lipofuscinose neuronal, sendo dois irmãos do tipo infantil tardio (Jansky-Bielschowsky) e um casal de irmãos do tipo juvenil (Spielmeyer-Sjögren). Uma autópsia e três biópsias corticais revelaram distensão de moderada a intensa dos neurônios por lipopigmentos, assim como gliose e atrofia cerebral generalizada. Acúmulo simi- lar foi também encontrado no baço, no fígado e no miocárdio. Os casos descritos são os primeiros da literatura brasileira em que o material de acúmulo foi identificado histoquimicamente como lipopigmento. Além de breve resumo da clínica da CLN, discutem-se problemas relativos à identificação da substância intraneuronal por histoquímica e microscopia eletrônica.

Neuronal ceroid-lipofuscinosis, a type of amaurotic family idiocy. Clinical and pathological study of four cases

Ceróide-lipofuscinose neuronal, um tipo de idiotia amaurótica familiar: estudo clínico-patológico de quatro casos

Luciano de Souza Queiroz^I; Joaquim N. da Cruz Neto^II; J. Lopes de Faria^III

^IFaculdade de Ciências Médicas da Universidade Estadual de Campinas. Intern, Dept. of Pathology

^IIFaculdade de Ciências Médicas da Universidade Estadual de Campinas. Resident, Dept. of Clinical Neurology and Neurosurgery (Late Chairman Prof. O. F. Julião)

^IIIFaculdade de Ciências Médicas da Universidade Estadual de Campinas. Chairman, Dept. of Pathology

SUMMARY

Neuronal ceroid-lipofuscinosis (NCL) is a recent term, proposed for acurate designation of the late-onset types of Amaurotic Family Idiocy (AFI).

Histopathology shows ubiquitous intraneuronal accumulation of lipopigments, being the most important factor for characterization of the entity at present time. Biochemical changes and pathogenesis are obscure. NCL is in contrast to the infantile type of AFI (Tay-Sachs disease), in which intraneuronal accumulation of gangliosides (sphingolipids) is due to the well known deficiency of a lysosomal enzyme.

The authors report on four cases of NCL, two brothers of the late infantile (Jansky-Bielschowsky) type and a brother and a sister of the juvenile (Spielmeyer-Sjögren) type. One autopsy and three cortical biopsies revealed moderate to severe distention of the neurons by lipopigment, with nerve cell loss, gliosis and cerebral atrophy. Lipopigment was also increased in liver, heart and spleen. The patients were the first in Brazilian literature in whom the storage material was identified as lipopigment by histochemical methods.

A brief summary of the clinical features of NCL is presented, and relevant problems are discussed, concerning interpretation of the nature of the storage material, and significance of the disease for gerontological research.

RESUMO

Estudos histoquímicos, bioquímicos e ultraestruturais permitiram recentemente distinguir dois tipos de entidades nosológicas dentre as doenças conhecidas como "Idiotia amaurótica familiar" (IAF). O primeiro, que inclue a doença de Tay-Sachs, ou tipo infantil de IAF, é constituido por doenças de armazenamento de gangliósides. Sua patogenia é conhecida, baseando-se em deficiências de enzimas lisossômicos. O segundo grupo, cuja patogenia é desconhecida, foi recentemente designado "Ceróide-lipofuscinose neuronal" (CLN) por Zeman e colaboradores. Corresponde aos tipos infantil tardio, juvenil e adulto de IAF, caracterizando-se histopatologicamente pelo acúmulo intraneuronal de lipopigmentos.

Os autores descrevem quatro casos de Ceróide-lipofuscinose neuronal, sendo dois irmãos do tipo infantil tardio (Jansky-Bielschowsky) e um casal de irmãos do tipo juvenil (Spielmeyer-Sjögren). Uma autópsia e três biópsias corticais revelaram distensão de moderada a intensa dos neurônios por lipopigmentos, assim como gliose e atrofia cerebral generalizada. Acúmulo simi- lar foi também encontrado no baço, no fígado e no miocárdio. Os casos descritos são os primeiros da literatura brasileira em que o material de acúmulo foi identificado histoquimicamente como lipopigmento.

Além de breve resumo da clínica da CLN, discutem-se problemas relativos à identificação da substância intraneuronal por histoquímica e microscopia eletrônica.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Address reprint requests to: Prof. J. Lopes de Faria Faculdade de Ciências Médicas Dept.º de Anatomia Patológica Caixa Postal 1170 18100 Campinas, SP Brazil.

Presented in part at the Fifth Brazilian Congress of Neurology, São Paulo, July 1972, and at the Neurological Meeting of the Associação Paulista de Medicina, São Paulo, October 1972. This study is dedicated to the memory of Prof. Oswaldo Freitas Julião.

Acknowledgements The authors are indebted to Dr. Alberto Pellegrini F.° for the clinical observation of case 3, to Dr. Nubor O. Facure for the cerebral biopsies, to Dr. Leoncio S. Queiroz F.° for the histopathologic description of the eye, and to Dr. and Mrs. John Cook Lane for revision of the manuscript. The skillful technical assistance of Mr. Ismael Vencio (histopathology) and Mr. Mauro Sanches (photographs) is greatly appreciated.

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2. ANDREWS, J. M.; SORESON, V.; CANCILLA, P. A.; PRICE, H. M. & MENKES, J. H. Late infantile neurovisceral storage disease with curvilinear bodies. Neurology (Minneapolis) 21:207, 1971.
3. von BAGH, K. & HORTLING, H. Blodfynd vid juvenil amaurotisk idioti. Nord. Med. 38:1072, 1948.
4. BAIN, A. D.; TATESON, R.; ANDERSON, J. M. & CUMINGS, J. N. Sandhoff's disease (GM-2 gangliosidosis, type 2) in a Scottish family. J. Ment. Def. Res. 16:119, 1972.
5. BENZ, U. U.; PEIFFER, J. & SCHLOTE, W. Morphologische und biochemische Untersuchungen über einen Fall von juveniler amaurotischer Idiotie (Neuronale Ceroid-Lipofuszinosis). Verh. Deutsch. Ges. Path. 55:427, 1971.
6. BIGNAMI, A.; PALLADINI, G. & BORRI, P. Neuronal lipidosis with visceral involvement in an adult. Acta Neuropathol. (Berlin) 12:50, 1969.
7. BJÖRKERUD, S. Isolated lipofuscin granules. A survey of a new field. Adv. Geront. Res. 1:257, 1964.
8. BOEHME, D. H.; COTTRELL, J. C; LEONBERG, S. C. & ZEMAN, W. Dominant form of neuronal ceroid-lipofuscinosis. Brain 94:745, 1971.
9. CARPENTER, S.; KARPATI, G.; WOLFE, L. S. & ANDERMANN, F. A type of juvenile cerebro-macular degeneration, characterized by granular osmiophilic deposits. J. Neurol. Sci. 18:67, 1973.
10. CAVANAGH, J. B. Batten's disease. A separate entity? Develop. Med. Child Neurol. 12:377, 1970.
11. DANTAS, A. M.; CURI, R. M.; GOMES, J. C. A.; INOCENTE, E. L.; GUEDES, J. B.; PAIVA, L. M. & ESTRADA, A. D. Doença de Spielmeyer-Vogt dois casos. Rev. Bras. Oftalmol. 30:87, 1971.
12. DERRY, D. M.; FAWCETT, J. S.; ANDERMANN, F. & WOLFE, L. S. Late infantile systemic lipidosis. Major monosialgangliosidosis. Delineation of two types. Neurology (Minneapolis) 18:340, 1968.
13. DUFFY, P. E.; KORNFELD, M. & SUZUKI, K. Neurovisceral storage disease with curvilinear bodies. J. Neuropath. Exp. Neurol. 27:351, 1968.
14. DUKE-ELDER, S. System of Ophthalmology. Vol. X, Diseases of the Retina. Henry Kimpton, London, 1967.
15. Editor's Note A new line on age pigment? Lancet 2:451, 1970.
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17. GONATAS, N. K.; GAMBETTI, P. & BAIRD, H. A second type of late infantile amaurotic idiocy with multilamellar cytosomes. J. Neuropath. Exp. Neurol. 27:371, 1968.
18. GONATAS, N. K.; TERRY, R. D.; WINKLER, R.; KOREY, S. R.; GOMEZ, C. J. & STEIN, A. A case of juvenile lipidosis: the significance of electron microscopic and biochemical observations of a cerebral biopsy. J. Neuropath. Exp. Neurol. 22:557, 1963.
19. GORDON, N. S.; MASSDEN, H. B. & NORONHA, M. J. Neuronal ceroid-lipofuscinosis (Batten's disease). Arch. Dis. Childh. 47:285, 1972.
20. GREEN, J. B. Neurophysiological studies in Batten's disease. Develop. Med. Child Neurol. 13:477, 1971.
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22. HALTIA, M.; RAPOLA, J.; SANTAVUORI, P. & KERÄNEN, A. Infantile type of so-called neuronal ceroid-lipofuscinosis: Part 2 Morphological and biochemical studies. J. Neurol. Sci. 18:269, 1973.
23. HERMANN, M. M.; RUBINSTEIN, J. L. & McKHANN, G. M. Additional electron microscopic observations on two cases of Batten-Spielmeyer-Vogt disease (Neuronal-ceroid-lipofuscinosis). Acta Neuropathol. (Berlin) 17:85, 1971.
24. JULIÃO, O. F.; CANELAS, H. M. & LONGO, N. A. Idiotia amaurótica familiar, forma juvenil. Estudo clínico e laboratorial de três casos. Arq. NeuroPsiquiat. (São Paulo) 14:136, 1956.
25. JULIÃO, O. F.; MAGALHÃES, P. B. & BRANDI, A. J. Moléstia de TaySachs. A propósito de três casos. Arq. Neuro-Psiquiat. (São Paulo) 2:359, 1944.
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Date of issue
Mar 1974

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ALENCAR, A. A. Forma juvenil da idiotia amaurótica familiar (doença de Spielmeyer-Vogt-Batten). Mem. Inst. Oswaldo Cruz (Rio de Janeiro) 70:353, 1972.

[2] 2. ANDREWS, J. M.; SORESON, V.; CANCILLA, P. A.; PRICE, H. M. & MENKES, J. H. Late infantile neurovisceral storage disease with curvilinear bodies. Neurology (Minneapolis) 21:207, 1971.

[3] 3. von BAGH, K. & HORTLING, H. Blodfynd vid juvenil amaurotisk idioti. Nord. Med. 38:1072, 1948.

[4] 4. BAIN, A. D.; TATESON, R.; ANDERSON, J. M. & CUMINGS, J. N. Sandhoff's disease (GM-2 gangliosidosis, type 2) in a Scottish family. J. Ment. Def. Res. 16:119, 1972.

[5] 5. BENZ, U. U.; PEIFFER, J. & SCHLOTE, W. Morphologische und biochemische Untersuchungen über einen Fall von juveniler amaurotischer Idiotie (Neuronale Ceroid-Lipofuszinosis). Verh. Deutsch. Ges. Path. 55:427, 1971.

[6] 6. BIGNAMI, A.; PALLADINI, G. & BORRI, P. Neuronal lipidosis with visceral involvement in an adult. Acta Neuropathol. (Berlin) 12:50, 1969.

[7] 7. BJÖRKERUD, S. Isolated lipofuscin granules. A survey of a new field. Adv. Geront. Res. 1:257, 1964.

[8] 8. BOEHME, D. H.; COTTRELL, J. C; LEONBERG, S. C. & ZEMAN, W. Dominant form of neuronal ceroid-lipofuscinosis. Brain 94:745, 1971.

[9] 9. CARPENTER, S.; KARPATI, G.; WOLFE, L. S. & ANDERMANN, F. A type of juvenile cerebro-macular degeneration, characterized by granular osmiophilic deposits. J. Neurol. Sci. 18:67, 1973.

[10] 10. CAVANAGH, J. B. Batten's disease. A separate entity? Develop. Med. Child Neurol. 12:377, 1970.

[11] 11. DANTAS, A. M.; CURI, R. M.; GOMES, J. C. A.; INOCENTE, E. L.; GUEDES, J. B.; PAIVA, L. M. & ESTRADA, A. D. Doença de Spielmeyer-Vogt dois casos. Rev. Bras. Oftalmol. 30:87, 1971.

[12] 12. DERRY, D. M.; FAWCETT, J. S.; ANDERMANN, F. & WOLFE, L. S. Late infantile systemic lipidosis. Major monosialgangliosidosis. Delineation of two types. Neurology (Minneapolis) 18:340, 1968.

[13] 13. DUFFY, P. E.; KORNFELD, M. & SUZUKI, K. Neurovisceral storage disease with curvilinear bodies. J. Neuropath. Exp. Neurol. 27:351, 1968.

[14] 14. DUKE-ELDER, S. System of Ophthalmology. Vol. X, Diseases of the Retina. Henry Kimpton, London, 1967.

[15] 15. Editor's Note A new line on age pigment? Lancet 2:451, 1970.

[16] 16. GEDIGK, P. & PIOCH, W. Über die formale Genese lipogener Pigmente. Untersuchungen mit Estern hochungesättigter Fettsäuren. Virchows Arch. 339: 100, 1965.

[17] 17. GONATAS, N. K.; GAMBETTI, P. & BAIRD, H. A second type of late infantile amaurotic idiocy with multilamellar cytosomes. J. Neuropath. Exp. Neurol. 27:371, 1968.

[18] 18. GONATAS, N. K.; TERRY, R. D.; WINKLER, R.; KOREY, S. R.; GOMEZ, C. J. & STEIN, A. A case of juvenile lipidosis: the significance of electron microscopic and biochemical observations of a cerebral biopsy. J. Neuropath. Exp. Neurol. 22:557, 1963.

[19] 19. GORDON, N. S.; MASSDEN, H. B. & NORONHA, M. J. Neuronal ceroid-lipofuscinosis (Batten's disease). Arch. Dis. Childh. 47:285, 1972.

[20] 20. GREEN, J. B. Neurophysiological studies in Batten's disease. Develop. Med. Child Neurol. 13:477, 1971.

[21] 21. HABERLAND, C.; BRUNNGRABER, E. G.; WITTING, L. A. & HOF, H. Late infantile amaurotic idiocy (LIAI). Neurology (Minneapolis) 22:305, 1972.

[22] 22. HALTIA, M.; RAPOLA, J.; SANTAVUORI, P. & KERÄNEN, A. Infantile type of so-called neuronal ceroid-lipofuscinosis: Part 2 Morphological and biochemical studies. J. Neurol. Sci. 18:269, 1973.

[23] 23. HERMANN, M. M.; RUBINSTEIN, J. L. & McKHANN, G. M. Additional electron microscopic observations on two cases of Batten-Spielmeyer-Vogt disease (Neuronal-ceroid-lipofuscinosis). Acta Neuropathol. (Berlin) 17:85, 1971.

[24] 24. JULIÃO, O. F.; CANELAS, H. M. & LONGO, N. A. Idiotia amaurótica familiar, forma juvenil. Estudo clínico e laboratorial de três casos. Arq. NeuroPsiquiat. (São Paulo) 14:136, 1956.

[25] 25. JULIÃO, O. F.; MAGALHÃES, P. B. & BRANDI, A. J. Moléstia de TaySachs. A propósito de três casos. Arq. Neuro-Psiquiat. (São Paulo) 2:359, 1944.

[26] 26. KLENK, E. Beiträge zur Chemie der Lipoidosen, Niemann-Picksche Krankheit und amaurotische Idiotie. Hoppe-Seylers Z. physiol. Chem. 262:128, 1939.

[27] 27. KORNFELD, M. Generalized lipofuscinosis (generalized Kufs' disease). J. Neuropath. Exp. Neurol. 31:668, 1972.

[28] 28. KRISTENSSON, K. & SOURANDER, P. Occurrence of lipofuscin in inherited metabolic disorders affecting the nervous system. J. Neurol. Neurosurg. Psychiat. 29:113, 1966.

[29] 29. LEVINE, A. S.; LEMIEUX, B.; BRUNNING, R.; WHITE, J. G.; SHARP, H. L.; STADLAN, E. & KRIVIT, W. Ceroid accumulation in a patient with progressive neurological disease. Pediatrics 42:483, 1968.

[30] 30. LEVY, J. A.; CANELAS, H. M.; JULIÃO, O. F.; MANISSADJIAN, A.; PILEGGI, F. L.; FRANÇA, L. C. M.; TENUTO, R. A. & DE JORGE, F. B. Idiotia amaurótica. Estudo clinico, bioquímico e histopatológico de quatro casos. Rev. Paul. Med. 67:171, 1965.

[31] 31. MARQUES, A. Idiotia amaurótica familiar. Estudo de um caso pessoal e revisão da casuística brasileira. Arq. Neuro-Psiquiat. (São Paulo) 1:207, 1943.

[32] 32. O'BRIEN, J. S. GM-1 Gangliosidoses. In Stanbury, J. B.; Wyngaarden, J. B. & Fredrickson, D. S. (eds.) The Metabolic Basis of Inherited Disease, 3^rd Ed. McGraw-Hill, New York, 1972.

[33] 33. O'BRIEN, J. S.; OKADA, S.; HO, M. W.; FILLERUP, D. L.; VEATH, M. L. & ADAMS, K. Ganglioside storage diseases. Fed. Proc. 30:956, 1971.

[34] 34. ODOR, D. L.; PEARCE, L. A. & JANEWAY, R. Juvenile amaurotic idiocy. An. electron microscopic study. Neurology (Minneapolis) 16:496, 1966.

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Brasil

Brasil

Neuronal ceroid-lipofuscinosis, a type of amaurotic family idiocy: clinical and pathological study of four cases

Ceróide-lipofuscinose neuronal, um tipo de idiotia amaurótica familiar: estudo clínico-patológico de quatro casos

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