What are optimal ceruloplasmin levels?

Optimal Ceruloplasmin Levels

Normal ceruloplasmin levels range from 20-60 mg/dL (200-600 mg/L), with levels below 20 mg/dL (200 mg/L) considered abnormal and requiring evaluation for Wilson's disease and other causes of hypoceruloplasminemia. 1, 2, 3

Normal Reference Range

• The standard normal range for ceruloplasmin is 20-60 mg/dL (200-600 mg/L) in adults and children over 6 months of age. 2, 4
• Infants younger than 6 months may have physiologically lower levels, with ceruloplasmin maintaining stable levels of 26-33 mg/dL after 6 months of age. 5
• Approximately 8.1% of healthy children may have ceruloplasmin levels below 20 mg/dL without disease, highlighting the importance of clinical context. 5

Diagnostic Thresholds for Wilson's Disease

• Ceruloplasmin below 20 mg/dL (200 mg/L) is the conventional diagnostic threshold for Wilson's disease, though this cutoff has limitations with a positive predictive value of only 8.4% and false-positive rate of 98.1% when used indiscriminately. 2, 6
• Extremely low levels below 5 mg/dL (50 mg/L) provide strong diagnostic evidence for Wilson's disease, with mean ceruloplasmin in Wilson's disease patients being 5.7 ± 4.7 mg/dL. 1, 2, 5
• A more optimal diagnostic cutoff of 15 mg/dL (150 mg/L) provides superior accuracy, with sensitivity of 95.6% and specificity of 95.5% in large hospital-based studies, compared to 99.0% sensitivity but only 80.9% specificity for the 20 mg/dL cutoff. 7
• For children specifically, a cutoff value of 16.8 mg/dL yields the highest diagnostic accuracy with 95.9% sensitivity and 93.6% specificity. 5

Important Physiologic Variations

• Gender differences exist: healthy boys have higher ceruloplasmin levels than healthy girls, and this pattern persists in asymptomatic Wilson's disease patients. 5
• Ceruloplasmin is an acute phase reactant and may be falsely elevated during pregnancy, inflammation, infection, malignant tumors, and inflammatory diseases, potentially masking Wilson's disease even when present. 2, 8
• Ceruloplasmin levels are elevated in infections (64.2 ± 3.2 mg/dL in surgical infections, 54.1 ± 2.6 mg/dL in medical infections) and malignancies (61.0 ± 3.0 mg/dL). 8

Critical Clinical Caveats

• Normal ceruloplasmin does NOT exclude Wilson's disease, as 10-20% of Wilson's disease patients have normal ceruloplasmin levels. 2
• Only 1.9% of Wilson's disease patients have ceruloplasmin above 20 mg/dL, making low levels highly sensitive but not specific. 5
• Other conditions causing low ceruloplasmin include: liver failure (53.0% have levels <20 mg/dL), nephrotic syndrome (37.7% have levels <20 mg/dL), copper deficiency, Menkes disease, and aceruloplasminemia. 1, 7
• Approximately 20% of heterozygous carriers for Wilson's disease have decreased ceruloplasmin (mean 25.6 ± 5.9 mg/dL) but do not have the disease. 2, 5

Monitoring During Treatment

• For adequately treated Wilson's disease patients, free serum copper should be maintained below 10 μg/dL, which is calculated as the difference between total serum copper and ceruloplasmin-bound copper. 1, 3
• Long-term monitoring should focus on free serum copper rather than ceruloplasmin levels alone, as ceruloplasmin may remain low despite effective treatment. 1