Neuronal Ceroid-lipofuscinosis with prominent chorea and without visual manifestations: a case report

Queiroz, Luciano de Souza; Cruz Neto, Joaquim Nogueira da

doi:10.1590/S0004-282X1979000100009

Abstracts

A case of neuronal ceroid-lipofuscinosis (NCL) is reported in a 11-year-old girl, whose main symptoms were progressive dementia since the age of 4 years and choreic movements since age 10. Seizures, myoclonus and visual deterioration were absent and optic fundi were normal. A cerebral biopsy disclosed two basic types of stored substance in the cytoplasm of neurons: a) severely balloned nerve cells in cortical layers HI and V contained a non-autofluorescent material, which stained with PAS and Sudan Black B in frozen, but not in paraffin sections; ultrastructurally, these neurons showed abundant corpuscles similar to the membranous cytoplasmic bodies of Tay-Sachs disease and, in smaller amounts, also zebra bodies; b) slightly distended or non-distended neurons in all layers contained lipopigment granules, which were autofluorescent, PAS-positive and sudanophil in both frozen and paraffin sections; their ultrastructure was closely comparable to that of lipofuscin. Similar bodies were found in the swollen segments of axons and in a few astrocytes and endothelial cells. The histochemical and ultrastructural demonstration of large amounts of lipopigments allows a presumptive classification of the case as NCL. However, the presence of involuntary movements, the absence of visual disturbances and the unusual ultrastructural features place the patient into a small heterogeneous group within the NCL. A better classification of such unique instances of the disease must await elucidation of the basic enzymatic defects.

É relatado um caso de ceróide-lipofuscinose neurônica, excepcional por suas características clínicas e ultraestruturais. Trata-se de menina de 11 anos, cujos principais sintomas foram demência progressiva de início aos 4 anos e movimentos coreicos na face e membros a partir dos 10 anos. Convulsões, mioclonias, deficiência visual e anormalidades fundoscópicas não foram observadas. Uma biópsia cerebral revelou basicamente: a) em neurônios de aspecto abalonado nas camadas corticais III e V, acúmulo de material não-fluorescente, que era PAS-positivo e Sudan Black B - positivo em cortes de congelação, porém que perdia estas propriedades após inclusão em parafina; ao microscópio eletrônico, tais neurônios revelaram corpúsculos intracitoplasmáticos semelhantes aos "membranous cytoplasmic bodies" da doença de Tay-Sachs e alguns "zebra bodies"; b) neurônios pouco ou não distendidos em todas as camadas corticais continham grânulos PAS-positivos, Sudan Black B-positivos e autofluorescentes tanto em cortes de parafina como de congelação, cuja ultraestrutura era semelhante à da lipofuscina. Corpúsculos análogos foram observados em alguns axônios, astrócitos e células endoteliais. A demonstração histoquímica e ultramicroscópica de grande quantidade de lipopigmentos no córtex cerebral permite-nos classificar o caso como ceróidelipofuscinose neurônica (CLN). Sua características ultraestruturais incomuns e peculiaridades clínicas como os movimentos coreicos e a falta de distúrbios visuais justificam porém situá-lo em um pequeno grupo especial nas CLN. Uma correta correta classificação só será possível após a descoberta dos defeitos enzimáticos responsáveis pela doença.

Neuronal Ceroid-lipofuscinosis with prominent chorea and without visual manifestations: a case report

Ceróide-lipofuscinose neurônica: estudo histoquímico e ultraestrutural de um caso com movimentos coreicos e sem distúrbios visuais

Luciano de Souza Queiroz^I; Joaquim Nogueira da Cruz Neto^II

^IPathologist. Department of Pathology (Chairman - Prof. Dr. J. Lopes de Faria), Faculdade de Ciências Médicas da Universidade Estadual de Campinas (UNICAMP), and the Instituto de Neurologia Clínica e Neurocirurgia de Limeira, SP

^IINeurologist. Department of Pathology (Chairman - Prof. Dr. J. Lopes de Faria), Faculdade de Ciências Médicas da Universidade Estadual de Campinas (UNICAMP), and the Instituto de Neurologia Clínica e Neurocirurgia de Limeira, SP

SUMMARY

A case of neuronal ceroid-lipofuscinosis (NCL) is reported in a 11-year-old girl, whose main symptoms were progressive dementia since the age of 4 years and choreic movements since age 10. Seizures, myoclonus and visual deterioration were absent and optic fundi were normal. A cerebral biopsy disclosed two basic types of stored substance in the cytoplasm of neurons: a) severely balloned nerve cells in cortical layers HI and V contained a non-autofluorescent material, which stained with PAS and Sudan Black B in frozen, but not in paraffin sections; ultrastructurally, these neurons showed abundant corpuscles similar to the membranous cytoplasmic bodies of Tay-Sachs disease and, in smaller amounts, also zebra bodies; b) slightly distended or non-distended neurons in all layers contained lipopigment granules, which were autofluorescent, PAS-positive and sudanophil in both frozen and paraffin sections; their ultrastructure was closely comparable to that of lipofuscin. Similar bodies were found in the swollen segments of axons and in a few astrocytes and endothelial cells.

The histochemical and ultrastructural demonstration of large amounts of lipopigments allows a presumptive classification of the case as NCL. However, the presence of involuntary movements, the absence of visual disturbances and the unusual ultrastructural features place the patient into a small heterogeneous group within the NCL. A better classification of such unique instances of the disease must await elucidation of the basic enzymatic defects.

RESUMO

É relatado um caso de ceróide-lipofuscinose neurônica, excepcional por suas características clínicas e ultraestruturais. Trata-se de menina de 11 anos, cujos principais sintomas foram demência progressiva de início aos 4 anos e movimentos coreicos na face e membros a partir dos 10 anos. Convulsões, mioclonias, deficiência visual e anormalidades fundoscópicas não foram observadas. Uma biópsia cerebral revelou basicamente: a) em neurônios de aspecto abalonado nas camadas corticais III e V, acúmulo de material não-fluorescente, que era PAS-positivo e Sudan Black B - positivo em cortes de congelação, porém que perdia estas propriedades após inclusão em parafina; ao microscópio eletrônico, tais neurônios revelaram corpúsculos intracitoplasmáticos semelhantes aos "membranous cytoplasmic bodies" da doença de Tay-Sachs e alguns "zebra bodies"; b) neurônios pouco ou não distendidos em todas as camadas corticais continham grânulos PAS-positivos, Sudan Black B-positivos e autofluorescentes tanto em cortes de parafina como de congelação, cuja ultraestrutura era semelhante à da lipofuscina. Corpúsculos análogos foram observados em alguns axônios, astrócitos e células endoteliais.

A demonstração histoquímica e ultramicroscópica de grande quantidade de lipopigmentos no córtex cerebral permite-nos classificar o caso como ceróidelipofuscinose neurônica (CLN). Sua características ultraestruturais incomuns e peculiaridades clínicas como os movimentos coreicos e a falta de distúrbios visuais justificam porém situá-lo em um pequeno grupo especial nas CLN. Uma correta correta classificação só será possível após a descoberta dos defeitos enzimáticos responsáveis pela doença.

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From the Department of Pathology (Chairman - Prof. Dr. J. Lopes de Faria), Faculdade de Ciências Médicas da Universidade Estadual de Campinas (UNICAMP), and the Instituto de Neurologia Clínica e Neurocirurgia de Limeira, SP. Presented at the XII Brazilian Congress of Pathology, Campinas, July 1977.

Acknowledgements - The Gleb Wataghin Institute of Physics (UNICAMP), through the courtesy of Dr. Sonotao Tsugahara, granted us the use of the electron microscope. Dr. Anamarli Nucci and Prof. Dr. J. Lopes de Faria kindly reviewed the manuscript.

Departamento de Anatomia Patológica - Faculdade de Ciências Médicas da UNICAMP - Caixa Postal 1170 - 13100 Campinas, SP - Brasil.

1. ALEU, F, P.; TERRY, R. D. & ZELLWEGER, H. - Electron microscopy of two cerebral biopsies in gargoylism. J. Neuropathol. Exp. Neurol. 24:304, 1965.
2. BRADY, R. O. - The sphingolipodystrophies. - In P. K. Bondy (ed.) - Duncan's Diseases of Metabolism. 6th. Ed. Saunders, Philadelphia, 1969.
3. CUMMINGS, J. F. & DE LAHUNTA, A. - An adult case of canine neuronal ceroid-lipofuscinosis. Acta Neuropathol. (Berlin) 39:43, 1977.
4. DAL CANTO, M. C.; RAPIN, I. & SUZUKI, K. - Neuronal storage disorders with chorea and curvilinear bodies. Neurology (Minneapolis) 24:1026, 1974.
5. DIEBOLD, K.; HÄFNER, H.; VOGEL, F. & SCHALT, E. - Die myoklonischen Varianten der familiaren amaurotischen Idiotie. Humangenetik 5:119, 1968.
6. ELFENBEIN, I. B. - Dystonic juvenile idiocy without amaurosis. A new syndrome. Light and electron microscopic observations of cerebrum. Johns Hopkins Med. J. 123:205, 1968.
7. HAGBERG, B.; HALTIA, M.; SOURANDER, P.; SVENNERHOLM, L. & EEGOLOFSSON, O. - Polyunsaturated fatty acid lipidosis. Infantile form of so-called neuronal ceroid-lipofuscinosis: I - Clinical and morphological aspects. Acta Paediat. Scand. 63:753, 1974.
8. HITTNER, H. M. & ZELLER, R. S. - Ceroid-lipofuscinosis (Batten's disease). Fluorescein angiography, electrophysiology, histopathology, ultrastructure, and a review of amaurotic familial idiocy. Arch. Ophthalmol. 93:178, 1975.
9. JENSEN, G. E.; CLAUSEN, J.; MELCHIOR, J. C. & KONAT, G. - Clinical, social and biochemical studies on Batten's syndrome, alias Spielmeyer-Vogt or Stengel's syndrome. Eur. Neurol. 15:203, 1977.
10. JERVIS, G. A. - Familial idiocy due to neuronal lipidosis (so-called late amaurotic idiocy). Am. J. Psychiat. 107:409, 1950.
11. JERVIS, G. A. & DONAHUE, S. - An unusual type of infantile lipofuscinosis. Acta Neuropathol. (Berlin) 31:109, 1975.
12. JERVIS, G. A. & PULLARKAT, R. K. - Pigment variant of lipofuscinosis. Neurology (Minneapolis) 28:500, 1978.
13. KIDD, M. - An electronmicroscopical study of a case of atypical cerebral lipidosis. Acta Neuropathol. (Berlin) 9:70, 1967.
14. MARQUES, A. - Dystonic form of amaurotic family idiocy. Report of a case. Arch. Neurol. Psychiat. (Chicago) 58:46, 1947.
15. MARTIN, J. J.; CEUTERICK, C. & EDGAR, G. W. F. - La céroïdo-lipofuscinose infantile généralisée (type Hagberg-Santavuori). A propos d'une nouvelle observation et de l'étude retrospective de deux autres cas. Acta Neurol. Belg. 76:103, 1976.
16. 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.
17. PELLISSIER, J. F.; HASSOUN, J.; GAMBARELLI, D.; TRIPIER, M. F.; ROGER. J. & TOGA, M. - Céroïde-lipofuscinose neuronale. Etude ultrastruturale de deux biopsies cérébrales. Acta Neuropathol. (Berlin) 28:353, 1974.
18. QUEIROZ, L. S.; DA CRUZ NETO, J. N. & DE FARIA, J. L. - Neuronal ceroid-lipofuscinosis, a type of amaurotic family idiocy. Clinical and pathological study of four cases. Arq. Neuro-Psiquiat. (São Paulo) 32:1, 1974.
19. REY-PIAS, J. M.; MORALES, C. & SERRATE, A. - The clinical classification of ceroid-lipofuscinosis. A statistical approach. Arch. Suisses Neurol. Neurochir. Psychiat. 119:19, 1976.
20. ROMEIS, B. - Mikroskopische Technik. R. Oldenbourg, München, 1948.
21. SAMORAJSKI, T.; ORDY, J. M. & KEEFE, J. R. - The fine structure of lipofuscin age pigment in the nervous system of aged mice. J. Cell Biol. 26:779, 1965.
22. SANTAVUORI, P.: HALTIA, M. & RAPOLA, J. - Infantile type of so-called neuronal ceroid-lipofuscinosis. Develop. Med. Child Neurol. 16:644, 1974.
23. STEFANINI, M.; DE MARTINO, C. & ZAMBONI, L. - Fixation of ejaculated spermatozoa for electron microscopy. Nature (London) 216:173, 1967.
24. STEKHOVEN, J. H. S. & VAN HAELST, U. J. G. M. - Ultrastructural study of so-called curvilinear bodies and fingerprint structures in lymphocytes in late-infantile amaurotic idiocy. Acta Neuropathol. (Berlin) 35:295, 1976.
25. TERRY, R. D. & WEISS, M. - Studies in Tay-Sachs disease: II. Ultrastructure of the cerebrum. J. Neuropathol. Exp. Neurol. 22:18, 1963.
26. TOWFIGHI, J.; BAIRD, H. W.; GAMBETTI, P. & GONATAS, N. K. - The significance of cytoplasmic inclusions in late infantile and juvenile amaurotic idiocy. Acta Neuropathol. (Berlin) 23:32, 1973.
27. WESTPHAL, A. & SIOLI, F. - Ueber einem unter dem Bilde einer doppelseitigen Athetose verluafenden Fall von Idiotie mit dem anatomischen Hirnbefund der juvenilen Form der amaurotischen Idiotie. Arch. f. Psychiat. 73:145, 1925.
28. ZEMAN, W. - Historical development of the nosological concept of amaurotic familial idiocy. In P. J. Vinken and G. W. Bruyn (eds.) - Handboook of Clinical Neurology. Vol. 10. North Holland, Amsterdam, 1970.
29. ZEMAN, W. - Morphologic approaches to the nosology of nervous system defects. In D. Bergsma (ed.) - The Second Conference on the Clinical Delineation of Birth Defects. Part VI, Nervous System. Williams & Wilkins, Baltimore, 1971.
30. ZEMAN, W.; DONAHUE, S.; DYKEN, P. & GREEN, J. - The neuronal ceroid-lipofuscinoses (Batten-Vogt syndrome). In P. J. Vinken and G. W. Bruyn (eds.) Handbook of Clinical Neurology. Vol. 10. North Holland, Amsterdam, 1970.
31. ZEMAN, W. & DYKEN, P. - Neuronal ceroid-lipofuscinosis (Batten's disease). Relationship to amaurotic family idiocy? Pediatrics 44:570, 1969.

Publication Dates

Publication in this collection
27 Aug 2012
Date of issue
Mar 1979

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

[1] 1. ALEU, F, P.; TERRY, R. D. & ZELLWEGER, H. - Electron microscopy of two cerebral biopsies in gargoylism. J. Neuropathol. Exp. Neurol. 24:304, 1965.

[2] 2. BRADY, R. O. - The sphingolipodystrophies. - In P. K. Bondy (ed.) - Duncan's Diseases of Metabolism. 6th. Ed. Saunders, Philadelphia, 1969.

[3] 3. CUMMINGS, J. F. & DE LAHUNTA, A. - An adult case of canine neuronal ceroid-lipofuscinosis. Acta Neuropathol. (Berlin) 39:43, 1977.

[4] 4. DAL CANTO, M. C.; RAPIN, I. & SUZUKI, K. - Neuronal storage disorders with chorea and curvilinear bodies. Neurology (Minneapolis) 24:1026, 1974.

[5] 5. DIEBOLD, K.; HÄFNER, H.; VOGEL, F. & SCHALT, E. - Die myoklonischen Varianten der familiaren amaurotischen Idiotie. Humangenetik 5:119, 1968.

[6] 6. ELFENBEIN, I. B. - Dystonic juvenile idiocy without amaurosis. A new syndrome. Light and electron microscopic observations of cerebrum. Johns Hopkins Med. J. 123:205, 1968.

[7] 7. HAGBERG, B.; HALTIA, M.; SOURANDER, P.; SVENNERHOLM, L. & EEGOLOFSSON, O. - Polyunsaturated fatty acid lipidosis. Infantile form of so-called neuronal ceroid-lipofuscinosis: I - Clinical and morphological aspects. Acta Paediat. Scand. 63:753, 1974.

[8] 8. HITTNER, H. M. & ZELLER, R. S. - Ceroid-lipofuscinosis (Batten's disease). Fluorescein angiography, electrophysiology, histopathology, ultrastructure, and a review of amaurotic familial idiocy. Arch. Ophthalmol. 93:178, 1975.

[9] 9. JENSEN, G. E.; CLAUSEN, J.; MELCHIOR, J. C. & KONAT, G. - Clinical, social and biochemical studies on Batten's syndrome, alias Spielmeyer-Vogt or Stengel's syndrome. Eur. Neurol. 15:203, 1977.

[10] 10. JERVIS, G. A. - Familial idiocy due to neuronal lipidosis (so-called late amaurotic idiocy). Am. J. Psychiat. 107:409, 1950.

[11] 11. JERVIS, G. A. & DONAHUE, S. - An unusual type of infantile lipofuscinosis. Acta Neuropathol. (Berlin) 31:109, 1975.

[12] 12. JERVIS, G. A. & PULLARKAT, R. K. - Pigment variant of lipofuscinosis. Neurology (Minneapolis) 28:500, 1978.

[13] 13. KIDD, M. - An electronmicroscopical study of a case of atypical cerebral lipidosis. Acta Neuropathol. (Berlin) 9:70, 1967.

[14] 14. MARQUES, A. - Dystonic form of amaurotic family idiocy. Report of a case. Arch. Neurol. Psychiat. (Chicago) 58:46, 1947.

[15] 15. MARTIN, J. J.; CEUTERICK, C. & EDGAR, G. W. F. - La céroïdo-lipofuscinose infantile généralisée (type Hagberg-Santavuori). A propos d'une nouvelle observation et de l'étude retrospective de deux autres cas. Acta Neurol. Belg. 76:103, 1976.

[16] 16. 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.

[17] 17. PELLISSIER, J. F.; HASSOUN, J.; GAMBARELLI, D.; TRIPIER, M. F.; ROGER. J. & TOGA, M. - Céroïde-lipofuscinose neuronale. Etude ultrastruturale de deux biopsies cérébrales. Acta Neuropathol. (Berlin) 28:353, 1974.

[18] 18. QUEIROZ, L. S.; DA CRUZ NETO, J. N. & DE FARIA, J. L. - Neuronal ceroid-lipofuscinosis, a type of amaurotic family idiocy. Clinical and pathological study of four cases. Arq. Neuro-Psiquiat. (São Paulo) 32:1, 1974.

[19] 19. REY-PIAS, J. M.; MORALES, C. & SERRATE, A. - The clinical classification of ceroid-lipofuscinosis. A statistical approach. Arch. Suisses Neurol. Neurochir. Psychiat. 119:19, 1976.

[20] 20. ROMEIS, B. - Mikroskopische Technik. R. Oldenbourg, München, 1948.

[21] 21. SAMORAJSKI, T.; ORDY, J. M. & KEEFE, J. R. - The fine structure of lipofuscin age pigment in the nervous system of aged mice. J. Cell Biol. 26:779, 1965.

[22] 22. SANTAVUORI, P.: HALTIA, M. & RAPOLA, J. - Infantile type of so-called neuronal ceroid-lipofuscinosis. Develop. Med. Child Neurol. 16:644, 1974.

[23] 23. STEFANINI, M.; DE MARTINO, C. & ZAMBONI, L. - Fixation of ejaculated spermatozoa for electron microscopy. Nature (London) 216:173, 1967.

[24] 24. STEKHOVEN, J. H. S. & VAN HAELST, U. J. G. M. - Ultrastructural study of so-called curvilinear bodies and fingerprint structures in lymphocytes in late-infantile amaurotic idiocy. Acta Neuropathol. (Berlin) 35:295, 1976.

[25] 25. TERRY, R. D. & WEISS, M. - Studies in Tay-Sachs disease: II. Ultrastructure of the cerebrum. J. Neuropathol. Exp. Neurol. 22:18, 1963.

[26] 26. TOWFIGHI, J.; BAIRD, H. W.; GAMBETTI, P. & GONATAS, N. K. - The significance of cytoplasmic inclusions in late infantile and juvenile amaurotic idiocy. Acta Neuropathol. (Berlin) 23:32, 1973.

[27] 27. WESTPHAL, A. & SIOLI, F. - Ueber einem unter dem Bilde einer doppelseitigen Athetose verluafenden Fall von Idiotie mit dem anatomischen Hirnbefund der juvenilen Form der amaurotischen Idiotie. Arch. f. Psychiat. 73:145, 1925.

[28] 28. ZEMAN, W. - Historical development of the nosological concept of amaurotic familial idiocy. In P. J. Vinken and G. W. Bruyn (eds.) - Handboook of Clinical Neurology. Vol. 10. North Holland, Amsterdam, 1970.

[29] 29. ZEMAN, W. - Morphologic approaches to the nosology of nervous system defects. In D. Bergsma (ed.) - The Second Conference on the Clinical Delineation of Birth Defects. Part VI, Nervous System. Williams & Wilkins, Baltimore, 1971.

[30] 30. ZEMAN, W.; DONAHUE, S.; DYKEN, P. & GREEN, J. - The neuronal ceroid-lipofuscinoses (Batten-Vogt syndrome). In P. J. Vinken and G. W. Bruyn (eds.) Handbook of Clinical Neurology. Vol. 10. North Holland, Amsterdam, 1970.

[31] 31. ZEMAN, W. & DYKEN, P. - Neuronal ceroid-lipofuscinosis (Batten's disease). Relationship to amaurotic family idiocy? Pediatrics 44:570, 1969.