Investigation of patients with possible Wilson disease
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Ceruloplasmin is an acute phase protein and a transport protein. This blue-colored glycoprotein belongs to the alpha 2-globulin electrophoretic fraction and contains 8 copper atoms per molecule.
Incorporation of copper into the structure occurs during the synthesis of ceruloplasmin in the hepatocytes. After secretion from the liver, ceruloplasmin migrates to copper-requiring tissue where the copper is liberated during catabolism of the ceruloplasmin molecule. In addition to transporting copper, ceruloplasmin has a catalytic function in the oxidation of iron (Fe[2+] to Fe[3+]), polyamines, catecholamines, and polyphenols.
Decreased concentrations occur during recessive autosomal hepatolenticular degeneration (Wilson disease). On a pathochemical level, the disease, which is accompanied by reduced ceruloplasmin synthesis, occurs as a consequence of missing Cu(2+) incorporation into the molecule due to defective metallothionein. This results in pathological deposits of copper in the liver (with accompanying development of cirrhosis), brain (with neurological symptoms), cornea (Kayser-Fleischer ring), and kidneys (hematuria, proteinuria, aminoaciduria). In homozygous carriers, ceruloplasmin levels are severely depressed. Heterozygous carriers exhibit either no decrease at all or just a mild decrease.
The rare Menkes syndrome is a genetically caused copper absorption disorder with concomitant lowering of the ceruloplasmin level. Protein loss syndromes and liver cell failures are the most important causes of acquired ceruloplasmin depressions.
As ceruloplasmin is a sensitive acute phase reactant, increases occur during acute and chronic inflammatory processes. Great increases can lead to a green-blue coloration of the sera.
See Wilson Disease Testing Algorithm in Special Instructions. Refer to The Diagnosis of Wilson Disease Mayo Medical Laboratories Communique 2005 Feb;30(2) for more information regarding diagnostic strategy.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
0-17 years: 14.0-41.0 mg/dL
> or =18 years: 15.0-30.0 mg/dL
0-17 years: 14.0-41.0 mg/dL
> or =18 years: 16.0-45.0 mg/dL
Values <14 mg/dL are expected in Wilson disease.
Values vary considerably from patient to patient and may be in the normal range in some patients with Wilson disease (indicating a different primary defect).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Ceruloplasmin levels are affected by infections (ceruloplasmin is a late acute phase reactant) and liver function.
Birth control pills and pregnancy increase ceruloplasmin levels.
Ceruloplasmin levels are not always extremely low in patients with Wilson disease.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
Cox DW, Tiimer Z, Roberts EA: Copper transport disorders: Wilson’s disease and Menkes disease. In Inborn Metabolic Disease. Edited by J Fernandes, JM Sandubray, F VandenBerghe. Berlin, Heidelberg, New York, Springer-Verlag, 2000, pp 385-391