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

Wilson Disease: Differential Diagnoses & Workup

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

Differential Diagnoses

Anemia, Chronic
Glycogen-Storage Disease Type V
Autoimmune Chronic Active Hepatitis
Glycogen-Storage Disease Type VI
Glycogen-Storage Disease Type 0
Glycogen-Storage Disease Type VII
Glycogen-Storage Disease Type I
Hepatitis A
Glycogen-Storage Disease Type II
Hepatitis B
Glycogen-Storage Disease Type III
Hepatitis C
Glycogen-Storage Disease Type IV

Other Problems to Be Considered

Cirrhosis
Multiple sclerosis
Huntington disease
Depression
Antisocial personality disorder
Parkinson disease
Leukodystrophy 
CNS vasculitis
Leigh disease
Neurodegenerative disease
a 1 -antitrypsin deficiency
Hereditary hemochromatosis

Workup

Laboratory Studies

  • Typical laboratory findings in patients with Wilson disease include the following:
    • Serum ceruloplasmin levels lower than 20 mg/dL
    • Low total serum copper levels
    • Increased urinary copper excretion (>100 mcg/d) 
  • The following laboratory findings may be observed in patients with Wilson disease:
    • Elevated aminotransferase levels
    • Abnormal coagulation test results
    • Hemolytic anemia
    • Aminoaciduria, glycosuria, uric aciduria, and calciuria

Imaging Studies

  • CT scans of the brain in patients with Wilson disease reveal hypodense regions in the basal ganglia (caudate nucleus, putamen, globus pallidus). Other possible findings include ventricular dilatation, brainstem atrophy, and posterior fossa atrophy. The extent of involvement as demonstrated on CT scans does not provide prognostic information.
  • Radiography is not uniformly recommended as part of the workup for Wilson disease in children because musculoskeletal abnormalities are rarely identified in the pediatric population.

Other Tests

  • Prenatal diagnosis based on DNA linkage analysis is currently available (see GeneTests for laboratories that provide genetic testing). The use of genetic testing can provide unequivocal confirmation of Wilson disease. However, because of the large size of the gene, genetic diagnosis can be challenging.
  • The family members of patients with Wilson disease should be biochemically or genetically screened. Monitoring and treatment of patients with asymptomatic Wilson disease is recommended. Linkage and mutational analysis are needed for prenatal diagnosis.

Procedures

  • Liver biopsy is the criterion standard for the diagnosis of Wilson disease.
  • In the context of the appropriate clinical picture, a hepatic copper content of more than 250 mcg dry weight of the liver confirms the diagnosis.
  • Copper stain test results are often negative early in the disease. Negative copper stain test results of liver biopsy specimens do not exclude the diagnosis because stored copper may be heterogenously distributed.

Histologic Findings

  • Laboratory findings in a hepatic section from a patient with severe Wilson disease reveals a proliferation of ductal structures, and histologic staining reveals copper deposition.

More on Wilson Disease

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

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  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/.

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Further Reading

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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

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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.

 
 
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