eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Wilson Disease: Treatment & Medication

Author: Beth A Carter, MD, Assistant Professor of Pediatrics, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Medical Director, Pediatric Intestinal Rehabilitation Program, Texas Children's Hospital and Baylor College of Medicine
Contributor Information and Disclosures

Updated: Nov 9, 2009

Treatment

Medical Care

  • Once Wilson disease is diagnosed, treatment is crucial to avoid a fatal outcome.
  • Medical treatment consists of various copper-chelating medications.
  • Ammonium tetrathiomolybdate forms complexes with ingested copper and forms complexes with copper and albumin in the blood. The use of ammonium tetrathiomolybdate is currently under investigation for the reduction of initial copper levels in patients with Wilson disease.

Surgical Care

  • Orthotopic liver transplantation is indicated in patients with Wilson disease with fulminant hepatic failure or disease that is worsening despite chelation therapy.4,5  

Consultations

  • Neurologist
  • Gastroenterologist
  • Ophthalmologist
  • Geneticist
  • Nutritionist
  • Surgeon (for transplantation, if indicated)

Diet

  • Dietary copper intake should be restricted.
  • Copper-containing foods include animal liver or kidneys, shellfish, chocolate, peas, unprocessed wheat, and dried beans.

Medication

Timely treatment with copper chelators is essential in patients with Wilson disease to decrease the likelihood of disease progression.6 Initiating chelation therapy in asymptomatic patients can prevent the deleterious effects of copper on the liver and CNS.

Other medications used to treat Wilson disease include anticholinergics, baclofen, GABA antagonists, and levodopa to treat parkinsonism and dystonia symptoms; antiepileptics to treat seizures; and neuroleptics to treat psychiatric symptoms. In addition, protein restriction, lactulose, or both are used to treat hepatic encephalopathy.

Chelating agents

These agents inhibit toxins by reacting with them to form a less active or inactive complex.


Penicillamine (Cuprimine, Depen)

Sulfur-containing degradation product of the antibiotic penicillin. Forms a soluble complex with copper that can be excreted by the kidney.

Adult

250 mg PO qid 1 h ac or 2 h pc

Pediatric

20 mg/kg/d PO divided qid 1 h ac or 2 h pc; not to exceed 1 g/d

Increases effects of immunosuppressants, phenylbutazone, and antimalarials; decreases digoxin effects; effects may decrease with coadministration of zinc salts, antacids, and iron

Documented hypersensitivity; renal insufficiency; previous penicillamine-related aplastic anemia or agranulocytosis

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Cross-allergenicity between penicillamine and penicillin is not universal, so may be cautiously administered to patients who are sensitive to penicillin; adverse reactions include fever, rash, leukopenia, lymphadenopathy, and thrombocytopenia (as many as 20% of patients); loss of gustatory sense and proteinuria rarely occur; serious but rare adverse effects include nephrotic syndrome and autoimmune dysfunction; respiratory symptoms, tinnitus, arthralgia, thyroiditis, optic neuritis, and nausea/vomiting have been reported; may interfere with vitamin B-6 metabolism (administer pyridoxine); if cesarean delivery or surgical procedure is anticipated, decrease dose because penicillamine may interfere with wound healing


Trientine (Syprine)

Effective PO chelator used to induce cupriuresis. Useful in patients unable to tolerate penicillamine.

Adult

1-1.5 g/d PO divided bid/qid 1 h ac or 2 h pc; not to exceed 2 g/d in divided doses

Pediatric

<12 years: 20 mg/kg PO divided bid/qid 1 h ac or 2 h pc; not to exceed 1.5 g/d
>12 years: Administer as in adults

Effects decrease with iron or other mineral supplements

Documented hypersensitivity; biliary cirrhosis; rheumatoid arthritis; cystinuria

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Contact dermatitis and iron deficiency anemia are the most common adverse effects; fever, epigastric pain, thrombocytopenia, and respiratory symptoms have been reported; separate administration of trientine and iron by at least 2 h to avoid interaction


Zinc acetate (Galzin)

Zinc salts induce intestinal metallothionein, which binds copper and prevents its passage into the blood stream. Use zinc as maintenance treatment in patients with Wilson disease who were treated initially with a copper chelator.

Adult

50 mg (as elemental) PO tid 1 h ac or 2 h pc

Pediatric

25 mg (as elemental) PO tid 1 h ac or 2 h pc

May impair absorption of tetracyclines and fluoroquinolones

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Do not use as initial treatment in Wilson disease because of length of time necessary before copper uptake is blocked; monitor effects via signs and symptoms of Wilson disease and 24-h urine copper levels; continuation of breastfeeding not recommended secondary to zinc-induced copper deficiency in infants; 24-h urine zinc levels can be used to measure compliance

More on Wilson Disease

Overview: Wilson Disease
Differential Diagnoses & Workup: Wilson Disease
Treatment & Medication: Wilson Disease
Follow-up: Wilson Disease
Multimedia: Wilson Disease
References
[ CLOSE WINDOW ]

References

  1. Wilson SA. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain. 1912;34:295.

  2. Stuehler B, Reichert J, Stremmel W, Schaefer M. Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients. J Mol Med. Sep 2004;82(9):629-34. [Medline].

  3. Stapelbroek JM, Bollen CW, van Amstel JK, et al. The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis. J Hepatol. Nov 2004;41(5):758-63. [Medline].

  4. Yoshitoshi EY, Takada Y, Oike F, Sakamoto S, Ogawa K, Kanazawa H. Long-term outcomes for 32 cases of Wilson's disease after living-donor liver transplantation. Transplantation. Jan 27 2009;87(2):261-7. [Medline].

  5. [Guideline] Murray KF, Carithers RL Jr. AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology. Jun 2005;41(6):1407-32. [Medline]. [Full Text].

  6. Leiros da Costa MD, Spitz M, Bacheschi LA, Leite CC, Lucato LT, Barbosa ER. Wilson's disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI. Neuroradiology. May 29 2009;[Medline].

  7. Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson's disease. Lancet. Feb 3 2007;369(9559):397-408. [Medline].

  8. Altschuler SM, Liacouras CA. Clinical Pediatric Gastroenterology. New York, NY: Churchill Livingstone; 1998:451-6.

  9. Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet. Dec 1993;5(4):327-37. [Medline].

  10. Das SK, Ray K. Wilson's disease: an update. Nat Clin Pract Neurol. Sep 2006;2(9):482-93. [Medline].

  11. Dhawan A, Taylor RM, Cheeseman P, De Silva P, Katsiyiannakis L, Mieli-Vergani G. Wilson's disease in children: 37-year experience and revised King's score for liver transplantation. Liver Transpl. Apr 2005;11(4):441-8. [Medline].

  12. Dhawan A, Taylor RM, Cheeseman P, et al. Wilson's disease in children: 37-year experience and revised King's score for liver transplantation. Liver Transpl. Apr 2005;11(4):441-8. [Medline].

  13. EuroWilson Project. EuroWilson. Living with Wilson's. Available at http://www.eurowilson.org.

  14. Gitlin JD. Aceruloplasminemia. Pediatr Res. Sep 1998;44(3):271-6. [Medline].

  15. Katzung BG. Basic and Clinical Pharmacology. 8th ed. Appleton & Lange; 2000.

  16. Manolaki N, Nikolopoulou G, Daikos GL, Panagiotakaki E, Tzetis M, Roma E. Wilson disease in children: analysis of 57 cases. J Pediatr Gastroenterol Nutr. Jan 2009;48(1):72-7. [Medline].

  17. McCullough AJ, Fleming CR, Thistle JL, et al. Diagnosis of Wilson's disease presenting as fulminant hepatic failure. Gastroenterology. Jan 1983;84(1):161-7. [Medline].

  18. McMillan JA, DeAngelis CD, Feigin RD, eds. Oski's Pediatrics: Principles and Practice. Baltimore, Md: Lippincott Williams & Wilkins; 1999:1721-2.

  19. Menkes JH. Menkes disease and Wilson disease: two sides of the same copper coin. Part II: Wilson disease. Eur J Paediatr Neurol. 1999;3(6):245-53. [Medline].

  20. National Digestive Diseases Information Clearinghouse (NDDIC). Available at http://digestive.niddk.nih.gov/ddiseases/pubs/wilson/.

  21. Oder W, Prayer L, Grimm G, et al. Wilson's disease: evidence of subgroups derived from clinical findings and brain lesions. Neurology. Jan 1993;43(1):120-4. [Medline].

  22. Roberts EA, Cox DW. Wilson disease. Baillieres Clin Gastroenterol. Jun 1998;12(2):237-56. [Medline].

  23. Schilsky ML, Scheinberg IH, Sternlieb I. Prognosis of Wilsonian chronic active hepatitis. Gastroenterology. Mar 1991;100(3):762-7. [Medline].

  24. Scott J, Gollan JL, Samourian S, Sherlock S. Wilson's disease, presenting as chronic active hepatitis. Gastroenterology. Apr 1978;74(4):645-51. [Medline].

  25. Tanzi RE, Petrukhin K, Chernov I, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet. Dec 1993;5(4):344-50. [Medline].

  26. Wilson's Disease Association. Available at http://www.wilsonsdisease.org/.

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Wilson disease, hepatolenticular degeneration, WD, Wilson's disease, ceruloplasmin, copper accumulation, copper metabolism dysfunction, CNS disorder, cirrhosis, liver disease, hepatic disease, Kayser-Fleischer rings, neurologic disorder, copper deposition

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Beth A Carter, MD, Assistant Professor of Pediatrics, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Medical Director, Pediatric Intestinal Rehabilitation Program, Texas Children's Hospital and Baylor College of Medicine
Beth A Carter, MD is a member of the following medical societies: American Gastroenterological Association, American Liver Foundation, and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
Disclosure: Nothing to disclose.

Medical Editor

Erawati V Bawle, MD, FAAP, FACMG, Division of Genetic and Metabolic Disorders, Children's Hospital of Michigan; Professor (Clinician-Educator), Department of Pediatrics, Wayne State University School of Medicine
Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Robert Anthony Saul, MD, Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center
Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.