Q:

What chemistry tests are used to diagnose Wilson's disease?

A:

In patients with Wilson's disease (WD), copper accumulation is chronic with clinical presentation usually between 6-40 years of age. Effects include hepatic cirrhosis, neurological disorders, Kayser-Fleischer rings, and hemolysis.

Tests:

Copper, Serum: Total serum copper levels vary with age, thus age specific reference intervals are provided. Healthy newborns have low serum copper concentrations. The levels increase in early childhood reaching an initial peak at about three to four years of age, then moderately decrease through adult years. After age 60, observed values may again increase. Total serum copper levels are typically below normal ranges for the Wilson’s disease patient, due likely to decreased ceruloplasmin concentrations. In diagnosing WD, it is recommended that Copper, serum be ordered as a component of the Copper-Ceruloplasmin Index assay.

Ceruloplasmin: Serum ceruloplasmin concentration is normally in the range of 25-63 mg/dL. In patients with Wilson’s disease, observed values are typically very low. However, a normal serum ceruloplasmin concentration is found in at least 5% of patients presenting neurological symptoms and up to 40% of patients with hepatic symptoms.

Copper-Ceruloplasmin Index: The copper index is a calculation to estimate the concentration of free copper unbound to ceruloplasmin. (Total serum copper in µg/dL) - (Ceruloplasmin in mg/dL x 3). Normal concentrations are 0-10 µg/dL.

Copper, Urine: Urinary copper excretion is almost invariably increased in the symptomatic patient, (usually exceeding 100 µg/day). Although random specimens may contain diagnostic information, a 24-hour collection is a more consistent indicator of copper urine.

Copper, Tissue: Hepatic copper concentration greater than 250 µg/g dry weight is usually found in Wilson’s disease, but may also be seen in other chronic liver disorders. In later stages of WD, copper is distributed unevenly in the liver and measurement of copper concentration is less reliable. In some patients with advanced liver disease, liver biopsy may be hazardous and thus contraindicated.

With each test, copper contaminated specimens can show an increased value. It is essential to observe specimen handling instructions and avoid specimen contact with all metal.

The definitive diagnosis of Wilson's disease may require additional information, such as identification of Kayser-Fleischer rings.