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Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease

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

Binnaz Ege

https://izlik.org/JA56AC96NX

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

https://izlik.org/JA56AC96NX

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 Research Article
Authors

Binnaz Ege This is me

Publication Date June 30, 1974
IZ https://izlik.org/JA56AC96NX
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. https://izlik.org/JA56AC96NX
AMA 1.Ege B. Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 1974;27(1-2):332-343. https://izlik.org/JA56AC96NX
Chicago Ege, Binnaz. 1974. “Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 27 (1-2): 332-43. https://izlik.org/JA56AC96NX.
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 [1]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, June 1974, [Online]. Available: https://izlik.org/JA56AC96NX
ISNAD Ege, Binnaz. “Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 27/1-2 (June 1, 1974): 332-343. https://izlik.org/JA56AC96NX.
JAMA 1.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, June 1974, pp. 332-43, https://izlik.org/JA56AC96NX.
Vancouver 1.Binnaz Ege. Effect of Penicillamine Therapy on Hepatic Lesions in Wilson Disease. Ankara Üniversitesi Tıp Fakültesi Mecmuası [Internet]. 1974 Jun. 1;27(1-2):332-43. Available from: https://izlik.org/JA56AC96NX