Degeneração hepatolenticular

Canelas, Horacio M.; Jorge, Francisco B. De; Escalante, Ovidio D.; Rocha-Qintão, Eder C.

doi:10.1590/S0004-282X1963000400001

Resumos

Após reverem os marcos fundamentais da história da moléstia de Wilson, os autores relatam 3 casos desta afecção. Dois pacientes faleceram, tendo o exame necroscópico confirmado o diagnóstico clínico-laboratorial. Entre as particularidades do quadro neurológico, sobressaía, em um caso, a existência de espasticidade em flexão e de sinais cerebelares. O anel corneano de Kayser-Fleischer apresentou-se sempre completo e bilateral. Entre os caracteres inconstantes do proteinograma do líquido cefalor-raqueano são salientadas a ausência de pré-albumina e os baixos níveis de globulinas ï„ƒ1 e ï„ƒ2. Provàvelmente pela primeira vez, foi observada redução dos valôres de fósforo e magnésio no sôro sangüíneo. O estudo das funções hepática e renal foi realizado por meio dos testes convencionais, tendo-se verificado que o comprometimento do fígado era discreto, em nítida desproporção com o grau de lesão histológica do órgão (cirrose pós-necrótica). Em relação aos rins, foi comprovada hiperaminacidúria em dois casos, associada a discreta diminuição da excreção tubular, em um deles. A análise genética pôde ser mais aprofundada em um dos casos, incluindo a pesquisa, nos seus familiares, do anel de Kayser-Fleischer, a determinação dos valôres de cobre no sangue e urina, e da ceruloplasminemia, além do estudo citogenético do paciente. O anel corneano foi comprovado em uma irmã assintomática, ocorrendo nela e em outros parentes nítidas alterações do metabolismo do cobre. O estudo do conteúdo de cobre nos tecidos confirmou os dados da literatura quanto ao acúmulo desse metal no pancreas, rins, supra-renais, fígado, substâncias branca e cinzenta do cérebro, tálamo, córtex cerebelar e núcleo lentículo-caudado, assim como níveis normais nas unhas e baixos nos cabelos. Verificação provàvelmente inédita foi o achado de acúmulo de cobre na substância negra e núcleo rubro, assim como nas glândulas submandibulares e no cerume. No líquido cefalorraqueano os valôres do cobre total se encontravam dentro dos limites normais e muito próximos dos do cobre de reação direta. Na bile, de acordo com as referências da literatura, observamos concentração de cobre normal na bile total e na fração B, e valôres diminuídos nas biles A e C. Em todos os casos verificou-se diminuição da concentração de cobre e ceruloplasmina no sangue e elevação dos valores na urina e saliva. O cobre de reação direta do soro, determinado em um caso, mostrou-se em nível relativamente alto. O estudo dos balanços metabólicos demonstrou positividade para o cobre nos períodos de contrôle, e discreta negatividade do balanço do fósforo. Após o emprego do BAL, e particularmente da D-penicilamina, o balanço do cobre se negativou e o do fósforo tornou-se mais acentuadamente negativo. Dieta hipocúprica, resinas permutadoras de cations ou sulfeto de potássio foram associados aos agentes complexantes. A melhora clínica, embora nítida no caso 3 após o uso de D-penicilamina e estrógenos, não correspondeu ao excelente resultado bioquímico.

After a review of the fundamental steps in the history of hepatolenticular degeneration, the authors report 3 cases of the disease. Two patients died, the post-mortem examination having confirmed the clinical and laboratorial diagnosis. Among the neurologic particularities the presence, in one case, of flexion spasticity and cerebellar signs, besides the usual picture of Wilson's disease, is stressed. The Kayser-Fleischer corneal ring was always complete and bilateral. Among the unsteady features of the proteinogram of the cerebrospinal fluid, absence of pre-albumin, and lowering of ï„ƒ1 and ï„ƒ2 globulins were more frequently found. Low blood phosphorus and magnesium contents were found in our cases, seemingly for the first time in the literature. Special attention was dedicated to the study of liver and kidney functions through the proper functional tests. The impairment of liver function was mild, in a striking disagreement with the degree of the histologic picture of post-necrotic cirrhosis. Regarding the kidney, in two cases increased urinary excretion of aminoacids was found, associated with a slightly lowered tubular excretion in one of them. The genetic study could be more detailed in one of the cases, and included the search for Kayser-Fleischer corneal ring, the determination of copper in blood and urine, and of blood ceruloplasmin in the relatives, besides the cytogenetic study of the patient. Kayser-Fleischer ring was found in an otherwise asymptomatic sister, and disorders of copper metabolism were evidenced in her and some other relatives. The study of copper contents in the tissues confirmed the data of the literature regarding the overload in pancreas, kidneys, adrenal glands, liver, white and gray matter of the brain, thalamus, cerebellar cortex, and in the lenticular and caudate nuclei, as well as normal levels in the nails and low contents in the hairs. Presumably for the first time, an increase of copper concentration in the substantia nigra and red nucleus, as well as in the submaxillary gland and cerumen, was found. In the cerebrospinal fluid the total copper content was very close to the direct reacting copper level, and fell into the normal range. In bile our data agree with the references in the literature, the copper content being normal in total bile and in B-fraction, and low in A and C-bile. Low blood copper and ceruloplasmin contents and increased copper concentration in urine and saliva were found in the three cases. Blood direct reacting copper was determined only in one case and showed a moderate increase. The study of the metabolic balance showed a positive result for copper in the control periods, and a slight negative result for phosphorus. After the use of BAL, and especially of D-penicillamine, the copper balance became negative and the phosphorus balance turned out markedly negative. Low copper diet, cation exchanging resins or potassium sulphide were associated with the metal binding agents in different therapeutic schemes. The clinical improvement, although noticeable in case 3 after the use of D-penicillamine and estrogens, did not agree with the gratifying biochemical results.

Horacio M. Canelas^I; Francisco B. De Jorge^II; Ovidio D. Escalante^III; Eder C. Rocha-Qintão^IV

^IAssistant professor; From the Departments of Neurology (Chairman: Prof. Adherbal Tolosa) and Medicine (Chairman: Prof. A. B. Ulhoa Cintra) of the University of São Paulo Medical School

^IIChief of the laboratory of the Department of Medicine; From the Departments of Neurology (Chairman: Prof. Adherbal Tolosa) and Medicine (Chairman: Prof. A. B. Ulhoa Cintra) of the University of São Paulo Medical School

^IIIFellow resident (El Salvador); From the Departments of Neurology (Chairman: Prof. Adherbal Tolosa) and Medicine (Chairman: Prof. A. B. Ulhoa Cintra) of the University of São Paulo Medical School

^IVResident of the Department of Medicine; From the Departments of Neurology (Chairman: Prof. Adherbal Tolosa) and Medicine (Chairman: Prof. A. B. Ulhoa Cintra) of the University of São Paulo Medical School

SUMMARY

After a review of the fundamental steps in the history of hepatolenticular degeneration, the authors report 3 cases of the disease. Two patients died, the post-mortem examination having confirmed the clinical and laboratorial diagnosis.

Among the neurologic particularities the presence, in one case, of flexion spasticity and cerebellar signs, besides the usual picture of Wilson's disease, is stressed. The Kayser-Fleischer corneal ring was always complete and bilateral. Among the unsteady features of the proteinogram of the cerebrospinal fluid, absence of pre-albumin, and lowering of ï₁ and ï₂ globulins were more frequently found. Low blood phosphorus and magnesium contents were found in our cases, seemingly for the first time in the literature.

Special attention was dedicated to the study of liver and kidney functions through the proper functional tests. The impairment of liver function was mild, in a striking disagreement with the degree of the histologic picture of post-necrotic cirrhosis. Regarding the kidney, in two cases increased urinary excretion of aminoacids was found, associated with a slightly lowered tubular excretion in one of them.

The genetic study could be more detailed in one of the cases, and included the search for Kayser-Fleischer corneal ring, the determination of copper in blood and urine, and of blood ceruloplasmin in the relatives, besides the cytogenetic study of the patient. Kayser-Fleischer ring was found in an otherwise asymptomatic sister, and disorders of copper metabolism were evidenced in her and some other relatives.

The study of copper contents in the tissues confirmed the data of the literature regarding the overload in pancreas, kidneys, adrenal glands, liver, white and gray matter of the brain, thalamus, cerebellar cortex, and in the lenticular and caudate nuclei, as well as normal levels in the nails and low contents in the hairs. Presumably for the first time, an increase of copper concentration in the substantia nigra and red nucleus, as well as in the submaxillary gland and cerumen, was found. In the cerebrospinal fluid the total copper content was very close to the direct reacting copper level, and fell into the normal range. In bile our data agree with the references in the literature, the copper content being normal in total bile and in B-fraction, and low in A and C-bile.

Low blood copper and ceruloplasmin contents and increased copper concentration in urine and saliva were found in the three cases. Blood direct reacting copper was determined only in one case and showed a moderate increase.

The study of the metabolic balance showed a positive result for copper in the control periods, and a slight negative result for phosphorus. After the use of BAL, and especially of D-penicillamine, the copper balance became negative and the phosphorus balance turned out markedly negative.

Low copper diet, cation exchanging resins or potassium sulphide were associated with the metal binding agents in different therapeutic schemes. The clinical improvement, although noticeable in case 3 after the use of D-penicillamine and estrogens, did not agree with the gratifying biochemical results.

RESUMO

Após reverem os marcos fundamentais da história da moléstia de Wilson, os autores relatam 3 casos desta afecção. Dois pacientes faleceram, tendo o exame necroscópico confirmado o diagnóstico clínico-laboratorial.

Entre as particularidades do quadro neurológico, sobressaía, em um caso, a existência de espasticidade em flexão e de sinais cerebelares. O anel corneano de Kayser-Fleischer apresentou-se sempre completo e bilateral. Entre os caracteres inconstantes do proteinograma do líquido cefalor-raqueano são salientadas a ausência de pré-albumina e os baixos níveis de globulinas ï₁ e ï₂. Provàvelmente pela primeira vez, foi observada redução dos valôres de fósforo e magnésio no sôro sangüíneo.

O estudo das funções hepática e renal foi realizado por meio dos testes convencionais, tendo-se verificado que o comprometimento do fígado era discreto, em nítida desproporção com o grau de lesão histológica do órgão (cirrose pós-necrótica). Em relação aos rins, foi comprovada hiperaminacidúria em dois casos, associada a discreta diminuição da excreção tubular, em um deles.

A análise genética pôde ser mais aprofundada em um dos casos, incluindo a pesquisa, nos seus familiares, do anel de Kayser-Fleischer, a determinação dos valôres de cobre no sangue e urina, e da ceruloplasminemia, além do estudo citogenético do paciente. O anel corneano foi comprovado em uma irmã assintomática, ocorrendo nela e em outros parentes nítidas alterações do metabolismo do cobre.

O estudo do conteúdo de cobre nos tecidos confirmou os dados da literatura quanto ao acúmulo desse metal no pancreas, rins, supra-renais, fígado, substâncias branca e cinzenta do cérebro, tálamo, córtex cerebelar e núcleo lentículo-caudado, assim como níveis normais nas unhas e baixos nos cabelos. Verificação provàvelmente inédita foi o achado de acúmulo de cobre na substância negra e núcleo rubro, assim como nas glândulas submandibulares e no cerume. No líquido cefalorraqueano os valôres do cobre total se encontravam dentro dos limites normais e muito próximos dos do cobre de reação direta. Na bile, de acordo com as referências da literatura, observamos concentração de cobre normal na bile total e na fração B, e valôres diminuídos nas biles A e C.

Em todos os casos verificou-se diminuição da concentração de cobre e ceruloplasmina no sangue e elevação dos valores na urina e saliva. O cobre de reação direta do soro, determinado em um caso, mostrou-se em nível relativamente alto.

O estudo dos balanços metabólicos demonstrou positividade para o cobre nos períodos de contrôle, e discreta negatividade do balanço do fósforo. Após o emprego do BAL, e particularmente da D-penicilamina, o balanço do cobre se negativou e o do fósforo tornou-se mais acentuadamente negativo.

Dieta hipocúprica, resinas permutadoras de cations ou sulfeto de potássio foram associados aos agentes complexantes. A melhora clínica, embora nítida no caso 3 após o uso de D-penicilamina e estrógenos, não correspondeu ao excelente resultado bioquímico.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

ACKNOWLEDGEMENTS

We wish to express our thanks to Dr. Fernando Teixeira-Mendes and Dr. Francisco Di Grado for the cytogenetic study of case 3.

1. ANDERSON, P. J.; POPPER, H. - Changes in hepatic structure in Wilson's disease. Amer. J. Path., 36:483-497, 1960.
2. BEARN, A. G. - Genetic and biochemical aspects of Wilson's disease. Amer. J. Med., 15:442-449, 1953.
3. BEARN, A.G. - Wilson's disease: an inborn error of metabolism with multiple manifestations. Amer. J. Med., 22:747-757, 1957.
4. BEARN, A. G.; KUNKEL, H. F. - Abnormalities of copper metabolism in Wilson's disease and their relationship to the aminoaciduria. J. clin. Invest., 33:400-409, 1954.
5. BEARN, A. G.; YU, T. F.; GUTMAN, A. B. - Renal function in Wilson's disease. J. clin. Invest., 36:1107-1114, 1957.
6. BICKEL, H.; NEALE, F. C; HALL, G. - A clinical and biochemical study of hepatolenticular degeneration (Wilson's disease). Quart. J. Med., 26: 527-558, 1957.
7. BLACK, D. A. K. - Renal Disease. Blackwell, Oxford, 1962, pág. 349.
8. CARTWRIGHT, G. E.; HODGES, R. E.; GUBLER, C. J.; MAHONEY, J. P.; DAUM, K.; WINTROBE, M. M.; BEAN, W. B. - Studies on copper metabolism. XIII: Hepatolenticular degeneration. J. clin. Invest., 33:1487-1501, 1954
9. CHOU, T.-P.; ADOLPH, W. H. - Copper metabolism in man. Biochem. J., 29:476-479, 1935.
10. CUMINGS, J. N. - The copper and iron content of brain and liver in normal and in hepato-lenticular degeneration. Brain, 71:410-415, 1948.
11. De JORGE, F. B.; CANELAS, H. M.; COSTA-SILVA, A. - Contribuição ao estudo do metabolismo do cobre. I: Metodologia da determinação do cobre em materiais biológicos. Rev. paul. Med., 61:350-355, 1962.
12. De JORGE, F. B.; CANELAS, H. M.; DIAS, J. C; CURY, L. - Studies on copper metabolism. III: Copper contents of saliva of normal subjects and of salivary glands and pancreas of autopsy material. Clin. chim. Acta, in press.
13. De JORGE, F. B.; CANELAS, H. M.; SPINA-FRANÇA, A. - Contribuição ao estudo do metabolismo do cobre. II: Valôres normais de cobre no sangue, líquido cefalorraqueano e urina. Rev. paul. Med., 62:125-128, 1963.
14. De JORGE, F. B.; CINTRA, A. B. U.; PAIVA, L. J.; CORRÊA, A. P.; NOVA, R. - On the chemistry of cerumen: ash, volatile substances, sodium, potassium, calcium, magnesium, phosphorus and copper. To be published.
15. DUCKETT, S.; FRANCE, N. E.; WALLIS, P. G. - Clinical and pathological findings in a case of hepatolenticular degeneration treated with penicillamin. J. Neurol. Neurosurg. Psychiat., 25:374-377, 1962.
16. FLEISCHER, B. - Zwei weitere Fälle von grünlicher Verfärbung der Kornea. Klin. Mbl. Augenheilk., 41:489-491, 1903.
17. FLEISCHER, B. - Die periphere braun-grünliche Hornhautverfärbung ais Symptom einer eigenartigen Allgemeinerkrankung. Munch, med. Wschr., 56:1120-1123, 1909.
18. FLEISCHER, B. - Über einer der "Pseudosklerose" naherstehender bisher unbekannte Krankheit. Dtsch. Z. Nervenheilk., 44:179-201, 1912.
19. GERLACH, W. - Untersuchungen über den Kupfergehalt menschlicher (und tieriescher) Organe. Virchows Arch. path. Anat., 294:171-197, 1934.
20. GERLACH, W.; ROHRSCHNEIDER, W. - Besteht das Pigment des Kayser-Fleischerschen Hornhautringes aus Silber? Klin. Wschr., 13:48-49, 1934.
21. GLAZEBROOK, A. J. - Wilson's disease. Edinb. med. J., 52:83-87, 1945.
22. GOLDBLUM, R. W.; DERBY, S.; LERNER, A. B. - The metal content of skin, nails and hair. J. invest. Derm., 20:13-18, 1953.
23. GOLDSTEIN, N. P.; RANDALL, R. N.; GROSS, J. B.; ROSEVEAR, J. W.; McGUCKIN, W. F. - Treatment of Wilson's disease (hepatolenticular degeneration) with DL-penicillamine. Neurology, 12:231-244, 1962.
24. GRASHCHENKOV, N. I.; HEKHT, B. M. - Copper content of brain tissues in health and in certain nervous diseases. Exp. Neurol., 2:573-580, 1960.
25. HALL, H. C. - La Dégénérescence Hépato-lenticulaire: Maladie de Wilson-Pseudosclérose. Masson, Paris, 1921.
26. HAUROWITZ, D. - Über eine Anomalie des Kupferstoffwechsels. Z. physiol. Chem., 190:72-74, 1930.
27. von HOESSLIN, C; ALZHEIMER, A. - Ein Beitrag zur Klinik und pathologischen Anatomie der Westphal-Strümpellschen Pseudosklerose. Z. ges. Neurol. Psychiat., 8:183-209, 1912.
28. HOLMBERG, C. G. - Development of knowledge of caeruloplasmin. In J. M. Walshe ■& J. N. Cumings: Wilson's Disease. Blackwell, Oxford, 1961, p. 64-68.
29. HOLMBERG, C. G.; LAURELL, C.-B. - Investigations in serum copper. II: Isolation of the copper containing protein, and a description of some of its properties. Acta chem. scand., 2:550-556, 1948.
30. KAYSER, A. - Über einen Fall von angeborenen grünlicher Verfärbung der Cornea. Klin. Mbl. Augenheilk. 40:22-25, 1902.
31. LANGE, J. - Über die Langzeitbehandlung des Morbus Wilson mit Penicillamin. Dtsch. Z. Nervenheilk., 183:63-77, 1962.
32. LüTHY, F. - über die hepato-lentikulàrer Degeneration (Wilson-Westphal-Strüm-pell). Dtsch. Z. Nervenheilk., 123:101-181, 1931.
33. MANDELBROTE, B. M.; STANIER, M. W.; THOMPSON, R. H. S.: THURSTON, M. N. - Studies on copper metabolism in demyelinating diseases of central nervous system. Brain, 71:212-228, 1948.
34. POLICARD, A.; BONNET, P.; BON AMOUR, G. - Étude histospectrographique de l'anneau cornéen de Kayser-Fleischer. C. r. Soc. Biol. (Paris), 120: 1120, 1936.
35. PORTER, H.; FOLCH, J. - Cerebrocuprein I: a copper-containing protein isolated from brain. J. Neurochem., 1:260-271, 1957.
36. van RAVESTEYN, A. H. - Metabolism of copper in man. Acta med. scand., 118:161-196, 1944.
37. RICE, E. W.; GOLDSTEIN, N. P. - Copper content of hair and nails in Wilson's disease (hepatolenticular degeneration). Metabolism, 10:1085-1087, 1961.
38. SALUS, R. - Grünliche Hornhautverfärbung bei multipler Sklerose. Med. Klin., 1:495-497, 1908.
39. SCHEINBERG, I.H.; GITLIN, D. - Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson's disease). Science, 116:484-485, 1952.
40. SHERLOCK, S. - Diseases of the Liver and Biliary System, ed. 2. Thomas, Springfield, 1958.
41. SILVA, L. C; GODOY, A.; KURBAN, S. T.; NEVES, D. P.; PONTES, J. F. - Estudo crítico dos testes de floculação: mecanismos e valor prático. Rev. Ass. méd. bras., 4:304-315, 1958.
42. SPIELMEYER, W. - Die histopathologischen Zusammengehörigkeit der Wilsonscher Krankheit und der Pseudosklerose. Z. ges. Neurol. Psychiat., 57:312-351, 1920.
43. STEIN, W. H.; BEARN, A. G.; MOORE, S. - The amino-acid content of the blood and urine in Wilson's disease. J. clin. Invest., 33:410-419, 1954.
44. STRÜM-PELL, A. - Über die Westphal'sche Pseudosklerose und Über diffuse Hirnsklerose, insbesonderer bei Kindern. Dtsch. Z. Nervenheilk. 12:115-149, 1898.
45. STRÜMPELL, A. - Ein weiterer Beitrag zur Kenntnis der sog. Pseudosklerose. Dtsch. Z. Nervenheilk., 14:348-355, 1899.
46. TAYLOR, W. J.; JACKSON, F. C; JENSEN, W. N. - Wilson's disease, portal hypertension and intrahepatic vascular obstruction. New Engl. J. Med., 260:1160-1164, 1959.
47. TU, J.; BLACKWELL, R. Q.; HOU, T. - Tissue copper levels in Chinese patients with Wilson's disease. Neurology, 13:155-159, 1963.
48. UZMAN, L. L. - Studies on mechanism of copper deposition in Wilson's disease. Arch. Neurol. Psychiat. (Chic), 77:164-165, 1957.
49. UZMAN, L. L.; DENNY-BROWN, D. - Aminoaciduria in hepatolenticular degeneration (Wilson's disease). Amer. J. med. Sci., 215:599-611, 1948.
50. UZMAN, L. L.; HOOD, B. - The familial nature of the amino-aciduria of Wilson's disease (hepato-lenticular degeneration). Amer. J. med. Sci., 223:392-400, 1952.
51. VOELSCH, M. - Beitrag zur Lehre von der Pseudosklerose. Dtsch. Z. Nervenheilk., 42:335-352, 1911.
52. WARREN, P. J.; EARL, C. J.; THOMPSON, R. H. S. - The distribution of copper in human brain. Brain, 83:709-717, 1960.
53. WESTPHAL, C. - über ein dem Bilde cerebrospinalen grauen Degeneration áhnlichen Erkrankung des central Nervensystems ohne anatomische Befunde, nebst einigen Bemerkungen über paradoxe Contraction. Arch. Psychiat. Nervenkr., 14:87-134, 1883.
54. WILSON, S. A. K. - Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain, 34:295-509, 1912.
55. ZIMDAHL, W. T.; HYMAN, I.; COOK, E. D. - Metabolism of copper in hepatolenticular degeneration. Neurology, 3:569-576, 1953.

Hepatolenticular degeneration clinical and biochemical study of three cases

Degeneração hepatolenticular: estudo clínico e bioquímico de três casos

Datas de Publicação

Publicação nesta coleção
21 Ago 2013
Data do Fascículo
Dez 1963

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

[1] 1. ANDERSON, P. J.; POPPER, H. - Changes in hepatic structure in Wilson's disease. Amer. J. Path., 36:483-497, 1960.

[2] 2. BEARN, A. G. - Genetic and biochemical aspects of Wilson's disease. Amer. J. Med., 15:442-449, 1953.

[3] 3. BEARN, A.G. - Wilson's disease: an inborn error of metabolism with multiple manifestations. Amer. J. Med., 22:747-757, 1957.

[4] 4. BEARN, A. G.; KUNKEL, H. F. - Abnormalities of copper metabolism in Wilson's disease and their relationship to the aminoaciduria. J. clin. Invest., 33:400-409, 1954.

[5] 5. BEARN, A. G.; YU, T. F.; GUTMAN, A. B. - Renal function in Wilson's disease. J. clin. Invest., 36:1107-1114, 1957.

[6] 6. BICKEL, H.; NEALE, F. C; HALL, G. - A clinical and biochemical study of hepatolenticular degeneration (Wilson's disease). Quart. J. Med., 26: 527-558, 1957.

[7] 7. BLACK, D. A. K. - Renal Disease. Blackwell, Oxford, 1962, pág. 349.

[8] 8. CARTWRIGHT, G. E.; HODGES, R. E.; GUBLER, C. J.; MAHONEY, J. P.; DAUM, K.; WINTROBE, M. M.; BEAN, W. B. - Studies on copper metabolism. XIII: Hepatolenticular degeneration. J. clin. Invest., 33:1487-1501, 1954

[9] 9. CHOU, T.-P.; ADOLPH, W. H. - Copper metabolism in man. Biochem. J., 29:476-479, 1935.

[10] 10. CUMINGS, J. N. - The copper and iron content of brain and liver in normal and in hepato-lenticular degeneration. Brain, 71:410-415, 1948.

[11] 11. De JORGE, F. B.; CANELAS, H. M.; COSTA-SILVA, A. - Contribuição ao estudo do metabolismo do cobre. I: Metodologia da determinação do cobre em materiais biológicos. Rev. paul. Med., 61:350-355, 1962.

[12] 12. De JORGE, F. B.; CANELAS, H. M.; DIAS, J. C; CURY, L. - Studies on copper metabolism. III: Copper contents of saliva of normal subjects and of salivary glands and pancreas of autopsy material. Clin. chim. Acta, in press.

[13] 13. De JORGE, F. B.; CANELAS, H. M.; SPINA-FRANÇA, A. - Contribuição ao estudo do metabolismo do cobre. II: Valôres normais de cobre no sangue, líquido cefalorraqueano e urina. Rev. paul. Med., 62:125-128, 1963.

[14] 14. De JORGE, F. B.; CINTRA, A. B. U.; PAIVA, L. J.; CORRÊA, A. P.; NOVA, R. - On the chemistry of cerumen: ash, volatile substances, sodium, potassium, calcium, magnesium, phosphorus and copper. To be published.

[15] 15. DUCKETT, S.; FRANCE, N. E.; WALLIS, P. G. - Clinical and pathological findings in a case of hepatolenticular degeneration treated with penicillamin. J. Neurol. Neurosurg. Psychiat., 25:374-377, 1962.

[16] 16. FLEISCHER, B. - Zwei weitere Fälle von grünlicher Verfärbung der Kornea. Klin. Mbl. Augenheilk., 41:489-491, 1903.

[17] 17. FLEISCHER, B. - Die periphere braun-grünliche Hornhautverfärbung ais Symptom einer eigenartigen Allgemeinerkrankung. Munch, med. Wschr., 56:1120-1123, 1909.

[18] 18. FLEISCHER, B. - Über einer der "Pseudosklerose" naherstehender bisher unbekannte Krankheit. Dtsch. Z. Nervenheilk., 44:179-201, 1912.

[19] 19. GERLACH, W. - Untersuchungen über den Kupfergehalt menschlicher (und tieriescher) Organe. Virchows Arch. path. Anat., 294:171-197, 1934.

[20] 20. GERLACH, W.; ROHRSCHNEIDER, W. - Besteht das Pigment des Kayser-Fleischerschen Hornhautringes aus Silber? Klin. Wschr., 13:48-49, 1934.

[21] 21. GLAZEBROOK, A. J. - Wilson's disease. Edinb. med. J., 52:83-87, 1945.

[22] 22. GOLDBLUM, R. W.; DERBY, S.; LERNER, A. B. - The metal content of skin, nails and hair. J. invest. Derm., 20:13-18, 1953.

[23] 23. GOLDSTEIN, N. P.; RANDALL, R. N.; GROSS, J. B.; ROSEVEAR, J. W.; McGUCKIN, W. F. - Treatment of Wilson's disease (hepatolenticular degeneration) with DL-penicillamine. Neurology, 12:231-244, 1962.

[24] 24. GRASHCHENKOV, N. I.; HEKHT, B. M. - Copper content of brain tissues in health and in certain nervous diseases. Exp. Neurol., 2:573-580, 1960.

[25] 25. HALL, H. C. - La Dégénérescence Hépato-lenticulaire: Maladie de Wilson-Pseudosclérose. Masson, Paris, 1921.

[26] 26. HAUROWITZ, D. - Über eine Anomalie des Kupferstoffwechsels. Z. physiol. Chem., 190:72-74, 1930.

[27] 27. von HOESSLIN, C; ALZHEIMER, A. - Ein Beitrag zur Klinik und pathologischen Anatomie der Westphal-Strümpellschen Pseudosklerose. Z. ges. Neurol. Psychiat., 8:183-209, 1912.

[28] 28. HOLMBERG, C. G. - Development of knowledge of caeruloplasmin. In J. M. Walshe ■& J. N. Cumings: Wilson's Disease. Blackwell, Oxford, 1961, p. 64-68.

[29] 29. HOLMBERG, C. G.; LAURELL, C.-B. - Investigations in serum copper. II: Isolation of the copper containing protein, and a description of some of its properties. Acta chem. scand., 2:550-556, 1948.

[30] 30. KAYSER, A. - Über einen Fall von angeborenen grünlicher Verfärbung der Cornea. Klin. Mbl. Augenheilk. 40:22-25, 1902.

[31] 31. LANGE, J. - Über die Langzeitbehandlung des Morbus Wilson mit Penicillamin. Dtsch. Z. Nervenheilk., 183:63-77, 1962.

[32] 32. LüTHY, F. - über die hepato-lentikulàrer Degeneration (Wilson-Westphal-Strüm-pell). Dtsch. Z. Nervenheilk., 123:101-181, 1931.

[33] 33. MANDELBROTE, B. M.; STANIER, M. W.; THOMPSON, R. H. S.: THURSTON, M. N. - Studies on copper metabolism in demyelinating diseases of central nervous system. Brain, 71:212-228, 1948.

[34] 34. POLICARD, A.; BONNET, P.; BON AMOUR, G. - Étude histospectrographique de l'anneau cornéen de Kayser-Fleischer. C. r. Soc. Biol. (Paris), 120: 1120, 1936.

[35] 35. PORTER, H.; FOLCH, J. - Cerebrocuprein I: a copper-containing protein isolated from brain. J. Neurochem., 1:260-271, 1957.

[36] 36. van RAVESTEYN, A. H. - Metabolism of copper in man. Acta med. scand., 118:161-196, 1944.

[37] 37. RICE, E. W.; GOLDSTEIN, N. P. - Copper content of hair and nails in Wilson's disease (hepatolenticular degeneration). Metabolism, 10:1085-1087, 1961.

[38] 38. SALUS, R. - Grünliche Hornhautverfärbung bei multipler Sklerose. Med. Klin., 1:495-497, 1908.

[39] 39. SCHEINBERG, I.H.; GITLIN, D. - Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson's disease). Science, 116:484-485, 1952.

[40] 40. SHERLOCK, S. - Diseases of the Liver and Biliary System, ed. 2. Thomas, Springfield, 1958.

[41] 41. SILVA, L. C; GODOY, A.; KURBAN, S. T.; NEVES, D. P.; PONTES, J. F. - Estudo crítico dos testes de floculação: mecanismos e valor prático. Rev. Ass. méd. bras., 4:304-315, 1958.

[42] 42. SPIELMEYER, W. - Die histopathologischen Zusammengehörigkeit der Wilsonscher Krankheit und der Pseudosklerose. Z. ges. Neurol. Psychiat., 57:312-351, 1920.

[43] 43. STEIN, W. H.; BEARN, A. G.; MOORE, S. - The amino-acid content of the blood and urine in Wilson's disease. J. clin. Invest., 33:410-419, 1954.

[44] 44. STRÜM-PELL, A. - Über die Westphal'sche Pseudosklerose und Über diffuse Hirnsklerose, insbesonderer bei Kindern. Dtsch. Z. Nervenheilk. 12:115-149, 1898.

[45] 45. STRÜMPELL, A. - Ein weiterer Beitrag zur Kenntnis der sog. Pseudosklerose. Dtsch. Z. Nervenheilk., 14:348-355, 1899.

[46] 46. TAYLOR, W. J.; JACKSON, F. C; JENSEN, W. N. - Wilson's disease, portal hypertension and intrahepatic vascular obstruction. New Engl. J. Med., 260:1160-1164, 1959.

[47] 47. TU, J.; BLACKWELL, R. Q.; HOU, T. - Tissue copper levels in Chinese patients with Wilson's disease. Neurology, 13:155-159, 1963.

[48] 48. UZMAN, L. L. - Studies on mechanism of copper deposition in Wilson's disease. Arch. Neurol. Psychiat. (Chic), 77:164-165, 1957.

[49] 49. UZMAN, L. L.; DENNY-BROWN, D. - Aminoaciduria in hepatolenticular degeneration (Wilson's disease). Amer. J. med. Sci., 215:599-611, 1948.

[50] 50. UZMAN, L. L.; HOOD, B. - The familial nature of the amino-aciduria of Wilson's disease (hepato-lenticular degeneration). Amer. J. med. Sci., 223:392-400, 1952.

[51] 51. VOELSCH, M. - Beitrag zur Lehre von der Pseudosklerose. Dtsch. Z. Nervenheilk., 42:335-352, 1911.

[52] 52. WARREN, P. J.; EARL, C. J.; THOMPSON, R. H. S. - The distribution of copper in human brain. Brain, 83:709-717, 1960.

[53] 53. WESTPHAL, C. - über ein dem Bilde cerebrospinalen grauen Degeneration áhnlichen Erkrankung des central Nervensystems ohne anatomische Befunde, nebst einigen Bemerkungen über paradoxe Contraction. Arch. Psychiat. Nervenkr., 14:87-134, 1883.

[54] 54. WILSON, S. A. K. - Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain, 34:295-509, 1912.

[55] 55. ZIMDAHL, W. T.; HYMAN, I.; COOK, E. D. - Metabolism of copper in hepatolenticular degeneration. Neurology, 3:569-576, 1953.

Brasil

Brasil

Degeneração hepatolenticular

Hepatolenticular degeneration clinical and biochemical study of three cases: estudo clínico e bioquímico de três casos

Resumos

Hepatolenticular degeneration clinical and biochemical study of three cases

Datas de Publicação