What are normal ceruloplasmin (ceruloplasmin) levels?

Normal Ceruloplasmin Levels

Normal ceruloplasmin levels typically range between 0.15-0.2 g/L (15-20 mg/dL) at the lower limit to approximately 0.6 g/L (60 mg/dL) at the upper limit, with variations depending on the laboratory and measurement method used. 1

Reference Range Details

The normal concentration of ceruloplasmin varies based on several factors:

• Measurement method:

  • Enzymatic assays measure copper-dependent oxidase activity
  • Immunologic assays (radioimmunoassay, radial immunodiffusion, nephelometry) may overestimate levels by not distinguishing between apoceruloplasmin and holoceruloplasmin 1

• Age-related variations:

  • Infants (up to 6 months): Physiologically very low levels
  • Early childhood: Peak levels higher than adults (300-500 mg/L)
  • Adults: Standard reference range (typically 0.2-0.6 g/L or 20-60 mg/dL) 1, 2

• Sex differences:

  • Women: Generally higher upper reference values than men
  • Women under 50: Upper values around 45 mg/dL
  • Women over 50: Upper values decrease to below 30 mg/dL
  • Men: Upper values plateau around 25 mg/dL by age 25 2

Factors Affecting Ceruloplasmin Levels

Conditions that increase ceruloplasmin:

• Acute inflammation (ceruloplasmin is an acute phase reactant)
• Hyperestrogenemic states:
  • Pregnancy
  • Estrogen supplementation
  • Oral contraceptive use 1
• Heart failure 3

Conditions that decrease ceruloplasmin:

• Wilson's disease (typically <0.1 g/L or <10 mg/dL)
• Protein-losing conditions:
  • Renal protein loss
  • Enteric protein loss
  • Malabsorption syndromes
• Severe end-stage liver disease of any etiology
• Copper deficiency (e.g., during parenteral nutrition without trace elements)
• Menkes disease
• Aceruloplasminemia (complete absence of the protein) 1
• Approximately 20% of Wilson's disease heterozygotes 1

Clinical Significance

• An extremely low ceruloplasmin level (<50 mg/L or <5 mg/dL) strongly suggests Wilson's disease 1
• Modestly subnormal levels require further evaluation
• Normal ceruloplasmin levels do not exclude Wilson's disease:
  • Up to 50% of patients with hepatic Wilson's disease may have ceruloplasmin in the low-normal range
  • 15-36% of children with Wilson's disease have normal ceruloplasmin 1

Pitfalls in Interpretation

• Serum ceruloplasmin alone has poor positive predictive value (only 6%) as a screening test for Wilson's disease 4
• Overreliance on ceruloplasmin measurement can lead to unnecessary testing and healthcare resource waste 5
• The American Association for the Study of Liver Disease recommends ceruloplasmin screening only in patients aged 3-55 years with liver abnormalities of uncertain cause 5
• When Wilson's disease is suspected despite normal ceruloplasmin, additional tests should be performed:
  • 24-hour urinary copper excretion
  • Hepatic copper content
  • Slit-lamp examination for Kayser-Fleischer rings
  • Genetic testing 1, 6

For accurate interpretation of ceruloplasmin results, clinicians should consider the patient's age, sex, inflammatory status, and the specific assay method used by their laboratory.