Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease

Binnaz Ege

Research Article

Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease

Year 1974, Volume: 27 Issue: 1-2, 332 - 343, 30.06.1974

Abstract

A 3-year-old boy presented with isolated hepatomegaly, low serum ceruloplasmin (0.875 mg/dL), Kayser–Fleischer rings, and aminoaciduria. Liver function tests were normal. Ultrasound‐guided needle biopsies were performed before and after 9 months of daily penicillamine (250 mg) chelation and dietary copper restriction.

Pre-treatment light microscopy showed periportal fibrosis, mild lymphocytic infiltration, and focal vacuolar degeneration without cirrhosis. Histochemical staining confirmed copper deposition.

Electron microscopy revealed mitochondrial degeneration, numerous electron-dense granules near Golgi‐like vesicles, dilated granular endoplasmic reticulum, and abundant lipid droplets.

Post-treatment biopsies showed no progression of fibrotic changes, a modest reduction in electron-dense material, and a marked increase in lipid droplet accumulation. Clinical exam, ceruloplasmin level (2 mg/dL), and eye findings stabilized.

These findings suggest that penicillamine therapy can halt progression of early Presirotic liver lesions in Wilson disease but may not reverse established ultrastructural damage.

Keywords

Wilson disease , Penicillamine (cuprimine) therapy , Copper accumulation , Liver biopsy , Presinusoidal fibrosis , Vacuolar degeneration , Electron-dense inclusions , Golgi vesicles , Lipid granules

References

1. Bocquet L, Jérôme H, Turpin R. Les lésions hépatiques de la maladie de Wilson préclinique. *Sem. Hop. Paris.* 1967;43:351.
2. Danks DM, Stevens BJ. Diagnosis of Wilson’s disease in children with liver disease. *Lancet.* 1969;1:22.
3. Ege B, Karagöl U, Kılıçturgay K, İmamoğlu A. Microscopic and electron microscopic study of hepatocellular changes in Wilson’s cirrhosis in children. *Acta Med Turc.* 1971;8:128.
4. Ford FR. Hepatolenticular degeneration. In: *Diseases of the Nervous System in Infancy, Childhood and Adolescence.* 3rd ed. Philadelphia: Saunders; 1966:477.
5. Hsio DY. Inborn errors of metabolism: Ceruloplasmin deficiency (Wilson’s disease). In: *Year Book of Medical Publishers.* 2nd ed. Chicago; 1968: I.
6. Kehrer F. Zur Ätiologie und Nosologie der Pseudo-Sklerose-Westphal-Wilson. *2 Neurol Psychiatr.* 1930;129:488.
7. Nakano M, Tanaka K. Pathological study on the liver in Wilson’s disease. *Fukuoka Acta Med.* 1965;26:871.
8. Nelson WE, Vaughan VC, McKay RJ. *Nelson Textbook of Pediatrics.* 10th ed. Philadelphia: Saunders; 1975.
9. Scheinberg IH, Gitlin D. Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson’s disease). *Science.* 1952;116:484.
10. Schoffner F, Sternlieb I, Barka T, Popper H. Hepatocellular changes in Wilson’s disease: Histochemical and electron microscopic studies. *Am J Pathol.* 1962;41:315.
11. Silverberg M, Cellis SS. The liver in juvenile Wilson’s disease. *Pediatrics.* 1962;30:402.
12. Stowens D. Wilson’s disease. In: *Pediatric Pathology.* 2nd ed. Baltimore: Williams & Wilkins; 1966.
13. Uzman LL. Histochemical localization of copper with rubeanic acid. *Lab Invest.* 1956;5:299.
14. Uzman LL. Intrahepatic distribution of copper in hepatolenticular degeneration. *Arch Pathol.* 1957;64:464.
15. Walshe JM. Hepatolenticular degeneration. *Br Med Bull.* 1957;13:132.
16. Walshe JM. Wilson’s disease: The presenting symptoms. *Arch Dis Child.* 1962;37:253.
17. Williams AO. Studies on copper, ceruloplasmin, and cirrhosis in Wilson’s disease. *Br J Exp Pathol.* 1965;46:564.
18. Wilson SA. Progressive lenticular degeneration. A familial disease with cirrhosis of the liver. *Brain.* 1912;34:295.

Wilson Hastalığında Penisillamin Tedavisinin Karaciğer Lezyonlarına Etkisi

Year 1974, Volume: 27 Issue: 1-2, 332 - 343, 30.06.1974

Binnaz Ege

Abstract

3 yaşındaki erkek hastada izole hepatomegali, düşük serum ceruloplazmin (% 0,875), Kayser–Fleischer halkaları ve aminoasiduri ile Wilson hastalığı düşünüldü. Karaciğer fonksiyon testleri normalken, teşhisi doğrulamak için iğne biopsisi yapıldı.

Tedavi öncesi ışık mikroskopisi; periportal fibrozis, hafif lenfositik infiltrasyon ve odak vaküoler dejenerasyon gösterdi. Hücre içi bakır, özel boyama ile saptandı.

Elektron mikroskopisi; mitokondri dejenerasyonu, Golgi‐benzeri veziküller çevresinde çok sayıda elektron-dans inklüzyon, dilate granüler endoplazmik retikulum ve bol miktarda lipid damlacıkları ortaya koydu.

9 aylık penisillamin tedavisi ve diyet kısıtlamasından sonra yeniden yapılan biyopside; fibrozis ilerlemedi, elektron-dans inklüzyonlar azaldı, lipid birikimi arttı. Klinik muayene, ceruloplazmin (% 2) ve göz bulguları stabil kaldı.

Bu sonuçlar, penisillaminin Wilson hastalığındaki erken Presirotik karaciğer lezyonlarının ilerlemesini durdurduğunu, ancak yerleşmiş ultrastrüktürel değişiklikleri geri çevirmekte sınırlı olduğunu göstermektedir.

References

1. Bocquet L, Jérôme H, Turpin R. Les lésions hépatiques de la maladie de Wilson préclinique. *Sem. Hop. Paris.* 1967;43:351.
2. Danks DM, Stevens BJ. Diagnosis of Wilson’s disease in children with liver disease. *Lancet.* 1969;1:22.
3. Ege B, Karagöl U, Kılıçturgay K, İmamoğlu A. Microscopic and electron microscopic study of hepatocellular changes in Wilson’s cirrhosis in children. *Acta Med Turc.* 1971;8:128.
4. Ford FR. Hepatolenticular degeneration. In: *Diseases of the Nervous System in Infancy, Childhood and Adolescence.* 3rd ed. Philadelphia: Saunders; 1966:477.
5. Hsio DY. Inborn errors of metabolism: Ceruloplasmin deficiency (Wilson’s disease). In: *Year Book of Medical Publishers.* 2nd ed. Chicago; 1968: I.
6. Kehrer F. Zur Ätiologie und Nosologie der Pseudo-Sklerose-Westphal-Wilson. *2 Neurol Psychiatr.* 1930;129:488.
7. Nakano M, Tanaka K. Pathological study on the liver in Wilson’s disease. *Fukuoka Acta Med.* 1965;26:871.
8. Nelson WE, Vaughan VC, McKay RJ. *Nelson Textbook of Pediatrics.* 10th ed. Philadelphia: Saunders; 1975.
9. Scheinberg IH, Gitlin D. Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson’s disease). *Science.* 1952;116:484.
10. Schoffner F, Sternlieb I, Barka T, Popper H. Hepatocellular changes in Wilson’s disease: Histochemical and electron microscopic studies. *Am J Pathol.* 1962;41:315.
11. Silverberg M, Cellis SS. The liver in juvenile Wilson’s disease. *Pediatrics.* 1962;30:402.
12. Stowens D. Wilson’s disease. In: *Pediatric Pathology.* 2nd ed. Baltimore: Williams & Wilkins; 1966.
13. Uzman LL. Histochemical localization of copper with rubeanic acid. *Lab Invest.* 1956;5:299.
14. Uzman LL. Intrahepatic distribution of copper in hepatolenticular degeneration. *Arch Pathol.* 1957;64:464.
15. Walshe JM. Hepatolenticular degeneration. *Br Med Bull.* 1957;13:132.
16. Walshe JM. Wilson’s disease: The presenting symptoms. *Arch Dis Child.* 1962;37:253.
17. Williams AO. Studies on copper, ceruloplasmin, and cirrhosis in Wilson’s disease. *Br J Exp Pathol.* 1965;46:564.
18. Wilson SA. Progressive lenticular degeneration. A familial disease with cirrhosis of the liver. *Brain.* 1912;34:295.

There are 18 citations in total.

Details

Primary Language	English
Subjects	Pediatric Gastroenterology
Journal Section	Articles
Authors	Binnaz Ege This is me
Publication Date	June 30, 1974
Published in Issue	Year 1974 Volume: 27 Issue: 1-2

Cite

APA	Ege, B. (1974). Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 27(1-2), 332-343.
AMA	Ege B. Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease. Ankara Üniversitesi Tıp Fakültesi Mecmuası. June 1974;27(1-2):332-343.
Chicago	Ege, Binnaz. “Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 27, no. 1-2 (June 1974): 332-43.
EndNote	Ege B (June 1, 1974) Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease. Ankara Üniversitesi Tıp Fakültesi Mecmuası 27 1-2 332–343.
IEEE	B. Ege, “Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 27, no. 1-2, pp. 332–343, 1974.
ISNAD	Ege, Binnaz. “Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 27/1-2 (June1974), 332-343.
JAMA	Ege B. Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 1974;27:332–343.
MLA	Ege, Binnaz. “Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 27, no. 1-2, 1974, pp. 332-43.
Vancouver	Ege B. Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 1974;27(1-2):332-43.