From the Guidelines
Ceruloplasmin levels are typically decreased in Wilson's disease, with levels usually below 20 mg/dL, and should be interpreted alongside other tests for accurate diagnosis. The measurement of ceruloplasmin is crucial in the diagnosis of Wilson's disease, as it is the major carrier for copper in the blood, accounting for 90% of the circulating copper in normal individuals 1. However, it is essential to note that serum ceruloplasmin concentrations can be elevated by acute inflammation and in states associated with hyperestrogenemia, and can be low in certain other conditions with marked renal or enteric protein loss or with severe end-stage liver disease of any etiology 1.
Some key points to consider when interpreting ceruloplasmin levels in Wilson's disease include:
- Ceruloplasmin levels are physiologically very low in early infancy to the age of 6 months, peak at higher than adult levels in early childhood, and then settle to the adult range 1
- Low levels of ceruloplasmin can also be seen in patients with copper deficiency, Menkes disease, and aceruloplasminemia 1
- About 10-20% of Wilson's disease patients may have normal ceruloplasmin levels, particularly during acute liver inflammation when ceruloplasmin can rise as an acute phase reactant
- For accurate diagnosis, ceruloplasmin should be interpreted alongside other tests including 24-hour urinary copper excretion, hepatic copper concentration, and genetic testing for ATP7B mutations 1
It is also important to note that immunologic assays for ceruloplasmin may overestimate ceruloplasmin concentrations because they do not discriminate between apoceruloplasmin and holoceruloplasmin, making serum ceruloplasmin as a diagnostic criterion difficult to interpret 1. Therefore, ceruloplasmin measurement should be used as an initial screening test, but not in isolation to confirm or exclude Wilson's disease.
From the Research
Ceruloplasmin in Wilson's Disease
- Ceruloplasmin is a protein that plays a crucial role in the diagnosis of Wilson's disease, an inherited disorder of copper accumulation 2.
- A low serum ceruloplasmin level is considered a diagnostic test for Wilson's disease, but it is not always a reliable indicator, as some patients with Wilson's disease may have normal ceruloplasmin levels 3.
- Screening for Wilson's disease by determining serum ceruloplasmin levels in unselected patients with clinical or laboratory evidence of liver disease is not feasible or cost-effective due to the low positive predictive value of low serum ceruloplasmin 4.
Diagnostic Steps
- Diagnostic steps for Wilson's disease include urine copper, blood ceruloplasmin, slit lamp examination for Kayser-Fleischer rings, and liver biopsy with quantitative copper assay 2.
- A strong family history and increased urinary and hepatic copper amounts can confirm the diagnosis of Wilson's disease, even in patients with normal ceruloplasmin levels 3.
Treatment Options
- Zinc is a treatment option for Wilson's disease, which reduces the toxic levels of circulating non-ceruloplasmin-bound copper by inducing intestinal metallothionein, blocking copper absorption, and increasing excretion in the stools 5.
- Zinc is recommended as a first-line treatment for neurological presentations and is gaining acceptance for hepatic presentations, with the advantages of low toxicity and minor side effects 5, 6.
- Other treatment options for Wilson's disease include D-penicillamine, trientine, and tetrathiomolybdate, which have varying degrees of effectiveness and safety profiles 2, 6.