Degeneração hepatolenticular: a propósito de 102 casos

Canelas, Horacio M.

doi:10.1590/S0004-282X1987000200014

Resumos

O autor descreve as características clínicas e laboratoriais de 102 casos de degeneração hepatolenticular (DHL) acompanhados no Departamento de Neurologia da Faculdade de Medicina da Universidade de São Paulo desde 1946. É analisado o problema do diagnóstico precoce dos familiares, a anatomia patológica da moléstia de Wilson é revista, e são examinadas as relações entre a DHL e outras moléstias hepatocerebrais. A etiopatogenia é discutida à luz das pesquisas mais recentes, sendo destacado o papel da redução da excreção biliar de cobre. A seguir são expostos os resultados do tratamento com D-penicilamina em 84 casos.

The author reports the clinical and laboratory findings in 102 patients of hepatolenticular degeneration (HLD) followed up in the Department of Neurology, University of São Paulo Medical School, since 1946. The problem of the early diagnosis of the relatives is analysed, the pathology of Wilson's disease is reviewed, and the relationship of HLD with other hepatocerebral diseases is examined. Etiopathogenesis is discussed according to current researches, the role of the decreased biliary copper excretion being emphasized. The results of treatment with D-penicillamine in 84 cases are commented.

Degeneração hepatolenticular: a propósito de 102 casos

Hepatolenticular degeneration: a comprehensive review apropos of 102 cases

Horacio M. Canelas

Professor Titular - Trabalho do Departamento de Neurologia da Faculdade de Medicina da Universidade de São Paulo

RESUMO

O autor descreve as características clínicas e laboratoriais de 102 casos de degeneração hepatolenticular (DHL) acompanhados no Departamento de Neurologia da Faculdade de Medicina da Universidade de São Paulo desde 1946. É analisado o problema do diagnóstico precoce dos familiares, a anatomia patológica da moléstia de Wilson é revista, e são examinadas as relações entre a DHL e outras moléstias hepatocerebrais. A etiopatogenia é discutida à luz das pesquisas mais recentes, sendo destacado o papel da redução da excreção biliar de cobre. A seguir são expostos os resultados do tratamento com D-penicilamina em 84 casos.

SUMMARY

The author reports the clinical and laboratory findings in 102 patients of hepatolenticular degeneration (HLD) followed up in the Department of Neurology, University of São Paulo Medical School, since 1946. The problem of the early diagnosis of the relatives is analysed, the pathology of Wilson's disease is reviewed, and the relationship of HLD with other hepatocerebral diseases is examined. Etiopathogenesis is discussed according to current researches, the role of the decreased biliary copper excretion being emphasized. The results of treatment with D-penicillamine in 84 cases are commented.

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Full text available only in PDF format.

Clínica Neurológica, FMUSP - Caixa Postal 3461 - 01000 - São Paulo, SP - Brasil.

1. Adams RD, Foley JM - The neurological disorders associated with liver disease. Res Pub Ass nervment Dis, 32:198-232, 1953.
2. Arioka I, Tanimukai H, Nishimura T, Nishinuma K, Ueda M - Histochemical study on hepatolenticular degeneration. Folia psychiat neurol jap., 17:373-380, 1963.
3. Azevedo EM, Scaff M, Barbosa ER, Gouveia Neto AE, Canelas HM - Heart involvement in hepatolenticular degeneration. Acta neurol scand 58:296-303, 1978.
4. Baker AB - Discussion of the paper by Adams & Foley. Res Pub Ass Res nerv ment Dis 32:233-234, 1953.
5. Barka T. Sheuer PJ, Schaffner F, Popper H - Structural changes of liver cells in copper intoxication. Archs Path 78:331-349, 1964.
6. Bearn AG - Genetic and biochemical aspects of Wilson's disease. Am J Med, 15: 442-449, 1953.
7. Bearn AG, Kunkel HG - Abnormalities of copper metabolism in Wilson's disease and their relationship to the aminoaciduria. J clin Invest 33:400-409, 1954.
8. Beart RW Jr., Putnam CW, Porter KA, Starzl TE - Liver transplantation for Wilson's disease. Lancet ii:176-177, 1975.
9. Bickel H - Attempts at caeruloplasmin substituion in Wilson's disease. In Walshe JM & Cumings JN: Wilson's disease, Some Current Concepts. Blackwell, Oxford, 1961, pp 273-281.
10. Bickel H - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 249.
11. Van Bogaert L, Willocx E - Études anatomo-cliniques sur la dégénérescence hépatolenticulaire: forme portale de la maladie de Wilson, forme familiale de la pseudosclérose de Westphal-Strümpell. Revue neurol 66:461-497, 1936.
12. Boulding JE - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 249.
13. Boudin G, Pépin B - Osteoarticular changes in hepatolenticular degeneration. In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp.233-236.
14. Böttiger LE, Möllerborg H - Increased copper content of hypertrophic myocardium. Acta med scand 165:413-416, 1959.
15. Bramwell B - Clinical studies. X: Familial cirrhosis of the liver: four cases of acute fatal cirrhosis of the liver in the same family, the patients being' respectively nine, ten, fourteen, and fourteen years of age; suggestive relatonship to Wilson's progressive degeneration of the lenticular nucleus. Edinburgh med J 17:90-99, 1916.
16. Cançado ELR, Rocha MS, Barbosa ER, Scaff M, Cerri GG, Magalhães A, Canelas HM - Abdominal ultrasonography in hepatolenticular degeneration: a study of 33 patients. Arq. Neuro-Psiquiat., 45:131-136, 1987.
17. Canelas HM, Carvalho N, Scaff M, Vitule A, Barbosa ER, Azevedo EM - Osteo- arthropathy of hepatolenticular degeneration. Acta neurol scand, 57:491, 1978.
18. Canelas HM, de Jorge FB, Tognola WA - Metabolic balances of copper in patients with hepatolenticular degeneration submitted to vegetarian and mixed diets. J Neurol Neurosurg Psychiat, 30:371-373, 1967.
19. Carrico RJ, Deutsch HF, Beinert H, Orme-Johnson WH - Some properties of an apoceruloplasmin-like protein in human serum. J biol Chem, 244:4141-4146, 1969.
20. Cartwright GE, Hodges RE, Gubler CJ, Mahoney JP, Daum K, Wintrobe MM, Bean WB - Studies on copper metabolism. III: Hepatolenticular degeneration. J clin Invest 33:1.487-1501, 1954.
21. Cole M, Rutherford RB, Smith FO - Experimental ammonia encephalopathy in the primate. Archs Neurol, Chicago, 26:130-136, 1972.
22. Cumings JN - The copper and iron content of brain and liver in the normal and in hepatolenticular degeneration. Brain 71:410-415, 1948.
23. Cumings JN - Trace metals in the brain and in Wilson's disease. J clin Path. 21:1-7, 1968.
24. Cumings JN - Biochemistry of basal ganglia. In Vinken PJ & Bruyn GW: Handbook of Clinical Neurology, Vol. 6 (Disease of Basal Ganglia). North-Holland, Amsterdam, 1968, pp.116-132.
25. Denny-Brown D - Hepatolenticular degeneration (Wilson's disease): two different components. New Engl J Med 270:1149-1156, 1964.
26. Dubois RS, Rodgerson DO, Slovis TD, Hambridge KM, Bianchi TA - Triethylene-tetramine dihydrochloride in Wilson's disease. Lancet i:775, 1970.
27. Dubois RS, Rodgerson DO, Starzl TE - Copper metabolism in Wilson's disease: effects of liver transplantation. Resume des Communications, III eme Symposium International sur la Maladie de Wilson, Paris, 1973.
28. Eaglesfield P. - The chemistry of penicillamine. In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp 254-259.
29. Feller ER, Shumacher HR - Osteoarticular changes in Wilson's disease. Arthritis Rheum 15:259-266, 1972.
30. FITZPATRICK TB - Disorders of melanin metabolism. In Wintrobe MM, Thorn GW, Adams RD, Bennett IL, Braunwald E, Esselbacher KJ, Petersdorf RG: Harrison's Principles of Internal Medicine. McGraw-Hill, New York, ed. 6, 1970, pp 614-620.
31. Fleischer B - Zwei weitere Fälle von grünlicher Verfärbung der Kornea. Klin Mbl Augenheilk, 41:489-491, 1903.
32. Fleischer B - Die periphere braun-grünlich Hornhautverfärbung, als Symptom einer eigenartigen Allgemeinerkrankung. Münch med Wschr, 96:1120-1123, 1909.
33. Fleischer B - Über eine der «Pseudosklerose» nahestehende bisher unbekannte Krankheit (gekennzeichnet durch Tremor, psychische Störungen, bräunliche Pigmentierung bestimmter Gewebe, insbesondere auch der Hornhautperipherie, Lebercirrhose). Dt Z NervHeilk, 44:179-201, 1912.
34. Fleming CR, Dickson ER, Wahner HW, Hollen-Horst RW, McCall JT - Pigmented corneal rings in non-wilsonian liver disease. Ann intern Med, 86:285-288, 1977.
35. Francois R, Larbre F, Nicolás, Mallein, Ruitton-Ugliengo - Maladie de Wilson à forme hépatique pure chez un nourrison. Lyon med. 8:467-482, 1958.
36. Franglen GT - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 248.
37. Frommer D - The measurement of biliary copper secretion in human. Clin Sei, 42:26P, 1972.
38. Frommer D - The transport of copper in human and rat bile. Resume des Communications, III eme Symposium International sur la Maladie de Wilson, Paris, 1973.
39. Frommer D, Morris I, Sherlock S, Abrams I, Newman S - Kayser-Fleischer-like rings in patients without Wilson's disease. Gastroenterology, 72:1331-1335, 1977.
40. Goldstein NP, Tauxe WN, McCall JT, Randall RV, Gross JB - Wilson's disease (hepatolenticular degeneration) : treatment with penicillamine and changes in hepatic trapping of radioactive copper. Archs Neurol, Chicago, 24:391-400, 1971.
41. Grashchenkov NI, Hekht BM - Copper content of brain tissues in health and in certain nervous diseases. Expl Neurol 2:573-580, 1960.
42. Greenfield JG - Hepatolenticular degeneration (Wilson's disease). In Blackwood W, McMonemey WH, Meyer A, Norman RM, Russell DS: Greenfield's Neuropathology. Arnold, London, ed 2, 1965, pp 576-580.
43. Hall HC - La Dégénérescence Hépato-lenticulaire. Masson, Paris, 1921.
44. Haurowitz F - über eine Anomalie des Kupferstoffwechsels. Z physiol Chem, 190:72-74, 1930.
45. Holmberg CG, Daurell CB - 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.
46. Howell JS - Histochemical demonstration of copper in copper fed rats and in hepatolenticular degeneration. J Path Bact 77:473-484, 1959.
47. Kehrer F - Zur Ätiologie und Nosologie der Pseudosklerose Westphal-Wilson. Z ges Neurol Psychiat 129:488-542, 1930.
48. Leu ML, Strickland T, Wang CC, Chen TSN - Skin pigmentation in Wilson's disease. J Am med Ass, 211:1542, 1543, 1970.
49. Lumsden CE - Pathogenetic mechanisms in the leuco-encephalopathies, in anoxic-ischaemic processes, in disorders of the blood and in intoxications. In Vinken PJ & Bruyn GW: Handbook of Clinical Neurology, Vol. 9 (Multiple Sclerosis and other Demyelinating Diseases). North-Holland, Amsterdam, 3970, p.638.
50. Lundquist RR - Studies on the pathogenesis of hepatolenticular degeneration. Ill: The effect of copper on rat liver lysosomes. Am J Path 53:903-927, 1968.
51. Liithy F - Über die hepato-lentikuläre degeneration (Wilson-Strümpell). Dt Z NervHeilk, 123:101-181, 1931.
52. Mann T, Keilin D - Haemocuprein and hepatocuprein, copper-protein compounds of blood and liver in mammals. Proc R Soe, Ser B, 126:303-315, 1938.
53. Marecek A, Heyrovsky A, Volek V - The effect of long term treatment with penicillamine on the copper content in the liver in patients with Wilson's disease. Acta hepato-gastroent, 22:292-296, 1975.
54. Martin J P - Wilson's disease. In Vinken PJ & Bruyn GW: Handbook of Clinical Neurology, vol. 6 (Diseases of the Basal Ganglia). North-Holland, Amsterdam, 1968, pp 267-278.
55. Matsuda I, Holtzman NA - Detection of apoceruloplasmin by radioimmunoassay: preliminary results in copper deficiency, Wilson's disease and Menke's syndrome. Resume des Communications, III ème Symposium International sur la Maladie de Wilson, Paris, 1973.
56. Mindelzun R, Elkin M, Scheinberg IH, Sternlieb I - Skeletal changes in Wilson's disease: a radiological study. Radiology, 94:127-132, 1970.
57. Morell AG - Copper and proteins (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 52.
58. Morell AG, Irving RA, Sternlieb I, Scheinberg IH - Physical and chemical studies on ceruloplasmin. V: Metabolic studies on sialic acid-free ceruloplasmin in vivo. J biol Chem, 243:155-159, 1968.
59. Morell AG, Shapiro JR, Scheinberg IH - Copper binding protein from human liver. In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp36-42.
60. Mossakowski MJ, Krasnicka Z, Renhawek K - Contribution des études des cellules d'Opalski à la connaissance de la pathogénie des lesions du système nerveux central dans les maladies hépatocérébraies. Revue neurol 125:248, 1971.
61. Opalski A - über eine besondere Art von Gliazeelen bei der Wilson-Pseudosklerose--Gruppe. Z ges Neurol Psychiat, 124:420-425, 1930.
62. O'Reilly S, Pollycove M, Tono M, Herradora L - Abnormalities of copper in Wilson's disease. 11: The internal kinetics of copper. Archs Neurol, Chicago 24:481-488, 1971.
63. O'Reilly S, Strickland T, Weber PM, Beckner WN, Shipley L - Abnormalities of the physiology of copper in Wilson's disease. I: The whole-body turnover of copper. Archs Neurol, Chicago, 24:385-390, 1971.
64. O'Reilly S, Weber PM, Oswald M, Shipley L - Abnormalities of the physiology of copper in Wilson's disease. Ill: The excretion of copper. Archs Neurol, Chicago, 25:28-32, 1971.
65. Osborn SB, Walshe JM - Copper uptake by the liver: study of a Wilson's disease family. In Walshe JM & Cummings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp. 141-150.
66. Osborn SB, Walshe JM - Studies with radiocopper (64Cu) in Wilson's disease: the liver/thigh ratio. Clin Sci, 27:319-328, 1964.
67. Owen CA Jr, Dickson ER, Goldstein N, Baggentoss AH, McCall JT - Hepatic subcellular distribution of copper in primary biliary cirrhosis: comparison with other hyperhepatocupric states and review of the literature. Mayo Clin Proc. 52:73-80, 1977.
68. Palladini G, Conford A, Medolago L, Venturini G, Zelazek S, Pistone A - Riproduzione experimentale della malattia de Wilson. Acta neurol 29:417-418, 1974.
69. Popper H - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 249.
70. Rosenoer VM, Michell RC - Skeletal changes in Wilson's disease (hepatolenticular degeneration). Br J Radiol, 32:805-809, 1959.
71. Sass-Kortsak A, Cherniak M, Geiger DW, Slater RJ - Observations on ceruloplasmin in Wilson's disease. J clin Invest, 38:1672-1682, 1959.
72. Scheinberg IH - Coper metabolism: a review. In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp 4-17.
73. Scheinberg IH - Further clinical aspects (Discussion). Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp 248-249.
74. Scheinberg IH - Discussão do trabalho de Bickel ⁹, pp 282-285.
75. Scheinberg IH, Gitlin D - Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson's disease). Science, NY, 116:484-485, 1952.
76. Scheinberg IH, Morell AG - Ceruloplasmin. In G. Eichhorn: Inorganic Biochemistry. Elsevier, Amsterdam, 1973, Vol. I, capit. 10, pp.306-319.
77. Scheinberg IH, Sternlieb I - The dual role of the liver in Wilson's disease. Med Clins N Am, 47:815-824, 1963.
78. Scheinberg IH, Sternlieb I - Wilson's Disease. Saunders, Philadelphia, 1984.
79. Scott J, Gollan JL, Samourian S, Sherlock S - Wilson's disease presenting as chronic active hepatitis. Gastroenterology, 74:645-651, 1978.
80. Sternlieb I - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 248.
81. Sternlieb I - Present status of diagnosis and prophylaxis of asymptomatic patients with Wilson's disease. In C M Leevy Diseases of the Diver and Biliary Tract. Karger, Basel, 1976, pp. 137-142.
82. Sternlieb I, Morell AG, Bauer CD, Combes B, De Bobes-Sternberg S, Scheinberg IH - Detection of the heterozygous carrier of the Wilson's disease gene. J elm Invest 40:707-715, 1961.
83.Sternlieb I, Morell AG, Scheinberg IH - Detection of the heterozygous carrier of the Wilson's disease gene. Resumo in J clin Invest, 38:1046, 1959.
84. Sternlieb I, Scheinberg IH - Prevention of Wilson's disease in asymptomatic patients. New Engl J Med, 278:352-359, 1968.
85. Strümpell A - über die Westphal'sche Pseudosklerose und über diffuse Hirnsklerose, insbesondere bei Kindern. Dt Z NervHeilk, 12:115-149, 1898.
86. Strümpell A - Ein weiterer Beitrag zur Kenntniss der sog. Pseudosklerose. Dt Z NervHeilk, 14:348-355, 1899.
87. Summer DW - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 249.
88. Sunderman FW Jr, White JC, Sunderman FW - Metabolie balance studies in hepatolenticular degeneration treated with diethyldithiocarbamate. Am J Med, 34:875-888, 1963.
89. Tu J, Blackwell RQ, Hou T - Tissue copper levels in Chinese patients with Wilson's disease. Neurology, Minneapolis, 13:155-159, 1963.
90. Uzman LL: Histochemical localization of copper with rubeanic acid. Lab Invest 5:299-305, 1956.
91. Uzman LL, Denny-Brown D - Amino-aciduria in hepatolenticular degeneration (Wilson's disease). Am J med Sei, 215:599-611, 1948.
92. Victor M, Adams RD, Cole M - The acquired (non-Wilsonian) type of chronic hepatolenticular degeneration. Medicine, Baltimore, 44:345-396, 1965.
93. Vierling JM, Shrager R, Rumble WF, Aamodt R, Berman MD, Jones EA - Incorporation of radiocopper into ceruloplasmin in normal subjects and in patients with primary biliary cirrhosis and Wilson's disease. Gastroenterology, 74:652-660, 1978.
94. Voelsch M - Beitrag zur Lehre von der Pseudosklerose (Westphal-Strümpell). Dt Z NervHeilk, 42:335-352, 1911.
95. Vogel FS, Klemper L - Biochemical reactions of cooper with neural mitochondria, with consideration of the role of the metal in the pathogenesis of Wilson's disease. Laborat Invest 12:171-179, 1963.
96. Walshe JM - Disturbance of aminoacid metabolism following- liver injury: a study by means of paper chromatography. Q Jl Med 22:483-505, 1953.
97. Walshe JM - Wilson's disease: new oral therapy. Lancet i:25-26, 1956.
98. Walshe JM - Penicillamine, a new oral therapy of Wilson's disease. Am J Med, 21:487-495, 1956.
99. Walshe JM - Management of penicillamine nephropathy in Wilson s disease: a new chelating- agent. Lancet, ii:1401-1402, 1969.
100. Walshe JM - Triethylenetetramine. Lancet i:154, 1970.
101. Walshe JM - Wilson's (hepatolenticular degeneration). In Vinken PJ, Bruyn GW & Klawans HL: Handbook of Clinical Neurology, Vol. 27 (Metabolic and Deficiency Diseases of the Nervous System), Part I. North-Holland, Amsterdam, 1976, p.379-414.
102. Watson DR - Copper metabolism: report of a case of Wilson's disease. J Am osteop Ass, 78:588-596, 1979.
103. Westphal C - über eine dem Bilde der cerebrospinalen grauen Degeneration ähnliche Erkrankung des centralen Nervensystems ohne anatomische Befund, nebst einigen Bemerkungen über paradoxe Contraction. Arch Psychiat Nervenkr, 14:87-134, 1883.
104. Wilson SAX - Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain, 34:295-507, 1912.
105. Zimdahl WT, Hyman I, Cook ED - Metabolism of copper in hepatolenticular degeneration. Neurology, Minneapolis, 3:569-576, 1953.

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Publicação nesta coleção
22 Jun 2011
Data do Fascículo
Jun 1987

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[1] 1. Adams RD, Foley JM - The neurological disorders associated with liver disease. Res Pub Ass nervment Dis, 32:198-232, 1953.

[2] 2. Arioka I, Tanimukai H, Nishimura T, Nishinuma K, Ueda M - Histochemical study on hepatolenticular degeneration. Folia psychiat neurol jap., 17:373-380, 1963.

[3] 3. Azevedo EM, Scaff M, Barbosa ER, Gouveia Neto AE, Canelas HM - Heart involvement in hepatolenticular degeneration. Acta neurol scand 58:296-303, 1978.

[4] 4. Baker AB - Discussion of the paper by Adams & Foley. Res Pub Ass Res nerv ment Dis 32:233-234, 1953.

[5] 5. Barka T. Sheuer PJ, Schaffner F, Popper H - Structural changes of liver cells in copper intoxication. Archs Path 78:331-349, 1964.

[6] 6. Bearn AG - Genetic and biochemical aspects of Wilson's disease. Am J Med, 15: 442-449, 1953.

[7] 7. Bearn AG, Kunkel HG - Abnormalities of copper metabolism in Wilson's disease and their relationship to the aminoaciduria. J clin Invest 33:400-409, 1954.

[8] 8. Beart RW Jr., Putnam CW, Porter KA, Starzl TE - Liver transplantation for Wilson's disease. Lancet ii:176-177, 1975.

[9] 9. Bickel H - Attempts at caeruloplasmin substituion in Wilson's disease. In Walshe JM & Cumings JN: Wilson's disease, Some Current Concepts. Blackwell, Oxford, 1961, pp 273-281.

[10] 10. Bickel H - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 249.

[11] 11. Van Bogaert L, Willocx E - Études anatomo-cliniques sur la dégénérescence hépatolenticulaire: forme portale de la maladie de Wilson, forme familiale de la pseudosclérose de Westphal-Strümpell. Revue neurol 66:461-497, 1936.

[12] 12. Boulding JE - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 249.

[13] 13. Boudin G, Pépin B - Osteoarticular changes in hepatolenticular degeneration. In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp.233-236.

[14] 14. Böttiger LE, Möllerborg H - Increased copper content of hypertrophic myocardium. Acta med scand 165:413-416, 1959.

[15] 15. Bramwell B - Clinical studies. X: Familial cirrhosis of the liver: four cases of acute fatal cirrhosis of the liver in the same family, the patients being' respectively nine, ten, fourteen, and fourteen years of age; suggestive relatonship to Wilson's progressive degeneration of the lenticular nucleus. Edinburgh med J 17:90-99, 1916.

[16] 16. Cançado ELR, Rocha MS, Barbosa ER, Scaff M, Cerri GG, Magalhães A, Canelas HM - Abdominal ultrasonography in hepatolenticular degeneration: a study of 33 patients. Arq. Neuro-Psiquiat., 45:131-136, 1987.

[17] 17. Canelas HM, Carvalho N, Scaff M, Vitule A, Barbosa ER, Azevedo EM - Osteo- arthropathy of hepatolenticular degeneration. Acta neurol scand, 57:491, 1978.

[18] 18. Canelas HM, de Jorge FB, Tognola WA - Metabolic balances of copper in patients with hepatolenticular degeneration submitted to vegetarian and mixed diets. J Neurol Neurosurg Psychiat, 30:371-373, 1967.

[19] 19. Carrico RJ, Deutsch HF, Beinert H, Orme-Johnson WH - Some properties of an apoceruloplasmin-like protein in human serum. J biol Chem, 244:4141-4146, 1969.

[20] 20. Cartwright GE, Hodges RE, Gubler CJ, Mahoney JP, Daum K, Wintrobe MM, Bean WB - Studies on copper metabolism. III: Hepatolenticular degeneration. J clin Invest 33:1.487-1501, 1954.

[21] 21. Cole M, Rutherford RB, Smith FO - Experimental ammonia encephalopathy in the primate. Archs Neurol, Chicago, 26:130-136, 1972.

[22] 22. Cumings JN - The copper and iron content of brain and liver in the normal and in hepatolenticular degeneration. Brain 71:410-415, 1948.

[23] 23. Cumings JN - Trace metals in the brain and in Wilson's disease. J clin Path. 21:1-7, 1968.

[24] 24. Cumings JN - Biochemistry of basal ganglia. In Vinken PJ & Bruyn GW: Handbook of Clinical Neurology, Vol. 6 (Disease of Basal Ganglia). North-Holland, Amsterdam, 1968, pp.116-132.

[25] 25. Denny-Brown D - Hepatolenticular degeneration (Wilson's disease): two different components. New Engl J Med 270:1149-1156, 1964.

[26] 26. Dubois RS, Rodgerson DO, Slovis TD, Hambridge KM, Bianchi TA - Triethylene-tetramine dihydrochloride in Wilson's disease. Lancet i:775, 1970.

[27] 27. Dubois RS, Rodgerson DO, Starzl TE - Copper metabolism in Wilson's disease: effects of liver transplantation. Resume des Communications, III eme Symposium International sur la Maladie de Wilson, Paris, 1973.

[28] 28. Eaglesfield P. - The chemistry of penicillamine. In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp 254-259.

[29] 29. Feller ER, Shumacher HR - Osteoarticular changes in Wilson's disease. Arthritis Rheum 15:259-266, 1972.

[30] 30. FITZPATRICK TB - Disorders of melanin metabolism. In Wintrobe MM, Thorn GW, Adams RD, Bennett IL, Braunwald E, Esselbacher KJ, Petersdorf RG: Harrison's Principles of Internal Medicine. McGraw-Hill, New York, ed. 6, 1970, pp 614-620.

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

[32] 32. Fleischer B - Die periphere braun-grünlich Hornhautverfärbung, als Symptom einer eigenartigen Allgemeinerkrankung. Münch med Wschr, 96:1120-1123, 1909.

[33] 33. Fleischer B - Über eine der «Pseudosklerose» nahestehende bisher unbekannte Krankheit (gekennzeichnet durch Tremor, psychische Störungen, bräunliche Pigmentierung bestimmter Gewebe, insbesondere auch der Hornhautperipherie, Lebercirrhose). Dt Z NervHeilk, 44:179-201, 1912.

[34] 34. Fleming CR, Dickson ER, Wahner HW, Hollen-Horst RW, McCall JT - Pigmented corneal rings in non-wilsonian liver disease. Ann intern Med, 86:285-288, 1977.

[35] 35. Francois R, Larbre F, Nicolás, Mallein, Ruitton-Ugliengo - Maladie de Wilson à forme hépatique pure chez un nourrison. Lyon med. 8:467-482, 1958.

[36] 36. Franglen GT - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 248.

[37] 37. Frommer D - The measurement of biliary copper secretion in human. Clin Sei, 42:26P, 1972.

[38] 38. Frommer D - The transport of copper in human and rat bile. Resume des Communications, III eme Symposium International sur la Maladie de Wilson, Paris, 1973.

[39] 39. Frommer D, Morris I, Sherlock S, Abrams I, Newman S - Kayser-Fleischer-like rings in patients without Wilson's disease. Gastroenterology, 72:1331-1335, 1977.

[40] 40. Goldstein NP, Tauxe WN, McCall JT, Randall RV, Gross JB - Wilson's disease (hepatolenticular degeneration) : treatment with penicillamine and changes in hepatic trapping of radioactive copper. Archs Neurol, Chicago, 24:391-400, 1971.

[41] 41. Grashchenkov NI, Hekht BM - Copper content of brain tissues in health and in certain nervous diseases. Expl Neurol 2:573-580, 1960.

[42] 42. Greenfield JG - Hepatolenticular degeneration (Wilson's disease). In Blackwood W, McMonemey WH, Meyer A, Norman RM, Russell DS: Greenfield's Neuropathology. Arnold, London, ed 2, 1965, pp 576-580.

[43] 43. Hall HC - La Dégénérescence Hépato-lenticulaire. Masson, Paris, 1921.

[44] 44. Haurowitz F - über eine Anomalie des Kupferstoffwechsels. Z physiol Chem, 190:72-74, 1930.

[45] 45. Holmberg CG, Daurell CB - 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.

[46] 46. Howell JS - Histochemical demonstration of copper in copper fed rats and in hepatolenticular degeneration. J Path Bact 77:473-484, 1959.

[47] 47. Kehrer F - Zur Ätiologie und Nosologie der Pseudosklerose Westphal-Wilson. Z ges Neurol Psychiat 129:488-542, 1930.

[48] 48. Leu ML, Strickland T, Wang CC, Chen TSN - Skin pigmentation in Wilson's disease. J Am med Ass, 211:1542, 1543, 1970.

[49] 49. Lumsden CE - Pathogenetic mechanisms in the leuco-encephalopathies, in anoxic-ischaemic processes, in disorders of the blood and in intoxications. In Vinken PJ & Bruyn GW: Handbook of Clinical Neurology, Vol. 9 (Multiple Sclerosis and other Demyelinating Diseases). North-Holland, Amsterdam, 3970, p.638.

[50] 50. Lundquist RR - Studies on the pathogenesis of hepatolenticular degeneration. Ill: The effect of copper on rat liver lysosomes. Am J Path 53:903-927, 1968.

[51] 51. Liithy F - Über die hepato-lentikuläre degeneration (Wilson-Strümpell). Dt Z NervHeilk, 123:101-181, 1931.

[52] 52. Mann T, Keilin D - Haemocuprein and hepatocuprein, copper-protein compounds of blood and liver in mammals. Proc R Soe, Ser B, 126:303-315, 1938.

[53] 53. Marecek A, Heyrovsky A, Volek V - The effect of long term treatment with penicillamine on the copper content in the liver in patients with Wilson's disease. Acta hepato-gastroent, 22:292-296, 1975.

[54] 54. Martin J P - Wilson's disease. In Vinken PJ & Bruyn GW: Handbook of Clinical Neurology, vol. 6 (Diseases of the Basal Ganglia). North-Holland, Amsterdam, 1968, pp 267-278.

[55] 55. Matsuda I, Holtzman NA - Detection of apoceruloplasmin by radioimmunoassay: preliminary results in copper deficiency, Wilson's disease and Menke's syndrome. Resume des Communications, III ème Symposium International sur la Maladie de Wilson, Paris, 1973.

[56] 56. Mindelzun R, Elkin M, Scheinberg IH, Sternlieb I - Skeletal changes in Wilson's disease: a radiological study. Radiology, 94:127-132, 1970.

[57] 57. Morell AG - Copper and proteins (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 52.

[58] 58. Morell AG, Irving RA, Sternlieb I, Scheinberg IH - Physical and chemical studies on ceruloplasmin. V: Metabolic studies on sialic acid-free ceruloplasmin in vivo. J biol Chem, 243:155-159, 1968.

[59] 59. Morell AG, Shapiro JR, Scheinberg IH - Copper binding protein from human liver. In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp36-42.

[60] 60. Mossakowski MJ, Krasnicka Z, Renhawek K - Contribution des études des cellules d'Opalski à la connaissance de la pathogénie des lesions du système nerveux central dans les maladies hépatocérébraies. Revue neurol 125:248, 1971.

[61] 61. Opalski A - über eine besondere Art von Gliazeelen bei der Wilson-Pseudosklerose--Gruppe. Z ges Neurol Psychiat, 124:420-425, 1930.

[62] 62. O'Reilly S, Pollycove M, Tono M, Herradora L - Abnormalities of copper in Wilson's disease. 11: The internal kinetics of copper. Archs Neurol, Chicago 24:481-488, 1971.

[63] 63. O'Reilly S, Strickland T, Weber PM, Beckner WN, Shipley L - Abnormalities of the physiology of copper in Wilson's disease. I: The whole-body turnover of copper. Archs Neurol, Chicago, 24:385-390, 1971.

[64] 64. O'Reilly S, Weber PM, Oswald M, Shipley L - Abnormalities of the physiology of copper in Wilson's disease. Ill: The excretion of copper. Archs Neurol, Chicago, 25:28-32, 1971.

[65] 65. Osborn SB, Walshe JM - Copper uptake by the liver: study of a Wilson's disease family. In Walshe JM & Cummings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp. 141-150.

[66] 66. Osborn SB, Walshe JM - Studies with radiocopper (64Cu) in Wilson's disease: the liver/thigh ratio. Clin Sci, 27:319-328, 1964.

[67] 67. Owen CA Jr, Dickson ER, Goldstein N, Baggentoss AH, McCall JT - Hepatic subcellular distribution of copper in primary biliary cirrhosis: comparison with other hyperhepatocupric states and review of the literature. Mayo Clin Proc. 52:73-80, 1977.

[68] 68. Palladini G, Conford A, Medolago L, Venturini G, Zelazek S, Pistone A - Riproduzione experimentale della malattia de Wilson. Acta neurol 29:417-418, 1974.

[69] 69. Popper H - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 249.

[70] 70. Rosenoer VM, Michell RC - Skeletal changes in Wilson's disease (hepatolenticular degeneration). Br J Radiol, 32:805-809, 1959.

[71] 71. Sass-Kortsak A, Cherniak M, Geiger DW, Slater RJ - Observations on ceruloplasmin in Wilson's disease. J clin Invest, 38:1672-1682, 1959.

[72] 72. Scheinberg IH - Coper metabolism: a review. In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp 4-17.

[73] 73. Scheinberg IH - Further clinical aspects (Discussion). Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, pp 248-249.

[74] 74. Scheinberg IH - Discussão do trabalho de Bickel ⁹, pp 282-285.

[75] 75. Scheinberg IH, Gitlin D - Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson's disease). Science, NY, 116:484-485, 1952.

[76] 76. Scheinberg IH, Morell AG - Ceruloplasmin. In G. Eichhorn: Inorganic Biochemistry. Elsevier, Amsterdam, 1973, Vol. I, capit. 10, pp.306-319.

[77] 77. Scheinberg IH, Sternlieb I - The dual role of the liver in Wilson's disease. Med Clins N Am, 47:815-824, 1963.

[78] 78. Scheinberg IH, Sternlieb I - Wilson's Disease. Saunders, Philadelphia, 1984.

[79] 79. Scott J, Gollan JL, Samourian S, Sherlock S - Wilson's disease presenting as chronic active hepatitis. Gastroenterology, 74:645-651, 1978.

[80] 80. Sternlieb I - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 248.

[81] 81. Sternlieb I - Present status of diagnosis and prophylaxis of asymptomatic patients with Wilson's disease. In C M Leevy Diseases of the Diver and Biliary Tract. Karger, Basel, 1976, pp. 137-142.

[82] 82. Sternlieb I, Morell AG, Bauer CD, Combes B, De Bobes-Sternberg S, Scheinberg IH - Detection of the heterozygous carrier of the Wilson's disease gene. J elm Invest 40:707-715, 1961.

[83] 83.Sternlieb I, Morell AG, Scheinberg IH - Detection of the heterozygous carrier of the Wilson's disease gene. Resumo in J clin Invest, 38:1046, 1959.

[84] 84. Sternlieb I, Scheinberg IH - Prevention of Wilson's disease in asymptomatic patients. New Engl J Med, 278:352-359, 1968.

[85] 85. Strümpell A - über die Westphal'sche Pseudosklerose und über diffuse Hirnsklerose, insbesondere bei Kindern. Dt Z NervHeilk, 12:115-149, 1898.

[86] 86. Strümpell A - Ein weiterer Beitrag zur Kenntniss der sog. Pseudosklerose. Dt Z NervHeilk, 14:348-355, 1899.

[87] 87. Summer DW - Further clinical aspects (Discussion). In Walshe JM & Cumings JN: Wilson's Disease, Some Current Concepts. Blackwell, Oxford, 1961, p. 249.

[88] 88. Sunderman FW Jr, White JC, Sunderman FW - Metabolie balance studies in hepatolenticular degeneration treated with diethyldithiocarbamate. Am J Med, 34:875-888, 1963.

[89] 89. Tu J, Blackwell RQ, Hou T - Tissue copper levels in Chinese patients with Wilson's disease. Neurology, Minneapolis, 13:155-159, 1963.

[90] 90. Uzman LL: Histochemical localization of copper with rubeanic acid. Lab Invest 5:299-305, 1956.

[91] 91. Uzman LL, Denny-Brown D - Amino-aciduria in hepatolenticular degeneration (Wilson's disease). Am J med Sei, 215:599-611, 1948.

[92] 92. Victor M, Adams RD, Cole M - The acquired (non-Wilsonian) type of chronic hepatolenticular degeneration. Medicine, Baltimore, 44:345-396, 1965.

[93] 93. Vierling JM, Shrager R, Rumble WF, Aamodt R, Berman MD, Jones EA - Incorporation of radiocopper into ceruloplasmin in normal subjects and in patients with primary biliary cirrhosis and Wilson's disease. Gastroenterology, 74:652-660, 1978.

[94] 94. Voelsch M - Beitrag zur Lehre von der Pseudosklerose (Westphal-Strümpell). Dt Z NervHeilk, 42:335-352, 1911.

[95] 95. Vogel FS, Klemper L - Biochemical reactions of cooper with neural mitochondria, with consideration of the role of the metal in the pathogenesis of Wilson's disease. Laborat Invest 12:171-179, 1963.

[96] 96. Walshe JM - Disturbance of aminoacid metabolism following- liver injury: a study by means of paper chromatography. Q Jl Med 22:483-505, 1953.

[97] 97. Walshe JM - Wilson's disease: new oral therapy. Lancet i:25-26, 1956.

[98] 98. Walshe JM - Penicillamine, a new oral therapy of Wilson's disease. Am J Med, 21:487-495, 1956.

[99] 99. Walshe JM - Management of penicillamine nephropathy in Wilson s disease: a new chelating- agent. Lancet, ii:1401-1402, 1969.

[100] 100. Walshe JM - Triethylenetetramine. Lancet i:154, 1970.

[101] 101. Walshe JM - Wilson's (hepatolenticular degeneration). In Vinken PJ, Bruyn GW & Klawans HL: Handbook of Clinical Neurology, Vol. 27 (Metabolic and Deficiency Diseases of the Nervous System), Part I. North-Holland, Amsterdam, 1976, p.379-414.

[102] 102. Watson DR - Copper metabolism: report of a case of Wilson's disease. J Am osteop Ass, 78:588-596, 1979.

[103] 103. Westphal C - über eine dem Bilde der cerebrospinalen grauen Degeneration ähnliche Erkrankung des centralen Nervensystems ohne anatomische Befund, nebst einigen Bemerkungen über paradoxe Contraction. Arch Psychiat Nervenkr, 14:87-134, 1883.

[104] 104. Wilson SAX - Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain, 34:295-507, 1912.

[105] 105. Zimdahl WT, Hyman I, Cook ED - Metabolism of copper in hepatolenticular degeneration. Neurology, Minneapolis, 3:569-576, 1953.