November 1, 2014
Penicillamine Test for the Diagnosis of Wilson's Disease Minimize

Penicillamine test for the diagnosis of Wilson's Disease

Indication

The diagnosis of Wilson's disease is difficult and should be made on a combination of investigations including serum copper (< 12 mmol/L), caeruloplasmin concentration (< 0.2 g/L) and 24 h urine copper excretion (> 1.25 mmol/24 hours). Some authorities believe that the copper concentration of liver tissue is the most important criterion but this may be compromised by the inherent difficulty in obtaining both appropriate reference material and adequate patient samples. Despite these investigations, the possibility of Wilson's disease may still be unclear and the test described may be of further use.

Contraindication

  1. The use of penicillamine prior to the investigation will compromise this test since it will have reduced the copper stores. Since the extent to which the stores will have been depleted is unknown, it would be prudent to avoid using this test within 6 months of penicillamine use.
  2. Known allergy to penicillamine.

Principle

Penicillamine solubilises copper and allows the stores to be excreted in the urine.

Side effects

Preparation

no special preparation required.

Requirements

  1. plain tube for blood sample
  2. 2 x 24h urine containers with no preservatives
  3. 2 x 500mg penicillamine tabs

Procedure

At least 2 baseline measurements of 24h urinary copper should be made prior to this test.

0900 h

take 10mL blood in plain container for serum copper and caeruloplasmin.
start 24 h urine collection for copper
administer 500mg D-Penicillamine

2100 h

administer a second dose of 500mg D-Penicillamine.

0900 h

complete 24h urine collection.

Interpretation

The diagnosis of Wilson's disease should be entertained in the absence of other diseases of the liver since the diagnostic accuracy of measurements of copper metabolism may be compromised by the presence of liver failure. The following threshold values are guidelines for Wilson's disease and a combination of abnormal results is probably necessary for a diagnosis to be made.

Caeruloplasmin

< 0.2 g/L

Serum copper

< 12 µmol/L

Urine copper

> 1.1 µmol / 24 h as an isolated test;
> 4 µmol is a more useful threshold

Urine copper post-penicillamine

> 25 µmol/24 h

Sensitivity and Specificity

Low serum caeruloplasmin may be seen in malnutrition, malabsorption and nephrotic syndrome as well as all forms of chronic liver disease esp PBC; and low serum copper may be disguised by an increase of up to 30% in inflammatory states.

If equivocal results are obtained from the penicillamine test, the next investigative step is to biopsy the liver to measure tissue copper content. This is so useful that some authorities believe that a liver copper measurement should be made on all diagnostic liver biopsies.

Reference

  • da Costa DM, Baldwin D, Portmann B, Lolin Y, Mowat A, Mieli-Vergani G. Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson's disease. Hepatology 1992;15:609-615.
  

Home|Paediatric|Endocrinology|Renal & electrolytes|Metabolic|Investigation protocols|Misc
Comments about this site to julian.barth@leedsth.nhs.uk Terms Of Use Privacy Statement