Wilson Disease

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Wilson Disease Testing Algorithm

Clinical Background

Wilson disease (also called hepatolenticular degeneration, Westphal-Struempell disease, Westphal pseudosclerosis) is an autosomal recessive inherited disorder of copper metabolism.

Epidemiology

Incidence - 1/30,000
Age - onset of symptoms prior to age 40

Inheritance

Autosomal recessive transmission
Caused by mutation in the ATP7B gene (located on chromosome V3)

Pathophysiology

Ceruloplasmin, a late acute phase reactant, is the principal copper-containing protein of plasma
Disease results from the absence or dysfunction of copper-transporting ATPases that reside in the trans-Golgi network of all cells
A variant P-type ATPase prevents incorporation of copper into ceruloplasmin, consequently elevating the concentration of circulating free copper
Excess copper is deposited in the kidneys, liver (where it causes cirrhosis), eyes (Kaiser-Fleischer rings) and brain (where it damages the basal ganglia)
Other conditions that prevent elimination of copper, such as biliary obstruction, may also lead to elevated free copper concentrations

Clinical Presentation

Ophthalmic manifestations
- Kayser-Fleischer rings (copper deposit on outer rim of cornea)
Hepatic manifestations - hepatitis, cirrhosis
Neurologic manifestations - movement disorders
- Dystonia
- Tremor
- Incoordination
- Bulbar and pseudobulbar palsies
- Psychiatric manifestations - behavioral disturbances, depression

Treatment

Prompt diagnosis is important since the treatment takes 3-6 months to have the desired effect.
Untreated Wilson disease can be fatal, subsequent to fulminant liver failure and/or brain damage

See Also

Alpha-1-Antitrypsin Deficiency - AAT

Hemochromatosis

Hepatitis B Virus - HBV

Hepatitis C Virus - HCV

Hepatitis, Autoimmune - AIH

Liver Disease Evaluation

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Wilson Disease Testing Algorithm

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Wilson Disease Screening Panel, Serum

ARUP #: 0020598

Methodology: Immunoturbidimetric/Inductively Coupled Plasma/Mass Spectrometry

Use:

Diagnose conditions of copper overload such as Wilson disease in symptomatic patients and/or patients with a family history of Wilson disease

Panel includes serum ceruloplasmin, serum copper and free serum copper. Other tests designed to support diagnosis of Wilson disease include 24-hour urine copper, hepatic copper, slit lamp examination for Kayser-Fleischer rings and genetic testing (ATP7B)

Limitations:

See individual component tests

Follow-up:

Test name: Copper, Urine

ARUP #: 0020461

Methodology: Inductively Coupled Plasma/Mass Spectrometry

Use:

Order to support diagnosis of Wilson disease and to monitor therapy in patient with Wilson disease

Limitations:

Follow-up:

Test name: Copper, Liver

ARUP #: 0020694

Methodology: Inductively Coupled Plasma/Mass Spectrometry

Use:

Order to support diagnosis of Wilson disease

Limitations:

Follow-up:

Test name: Copper, Serum

ARUP #: 0020096

Methodology: Inductively Coupled Plasma/Mass Spectrometry

Use:

This test is available alone or as part of a Wilson disease serum screening panel, which also includes serum ceruloplasmin and serum free copper

Limitations:

Serum copper may be elevated with infection, inflammation, stress, copper supplementation, oral contraceptives, and pregnancy

Concentrations are 2-3 times normal in the third trimester of pregnancy

Copper may be lowered with corticosteroids, zinc, malnutrition and malabsorption

Follow-up:

Test name: Copper, Serum Free (Direct)

ARUP #: 0020596

Methodology: Inductively Coupled Plasma/Mass Spectrometry

Use:

Order to support diagnosis of Wilson disease and to monitor therapy in patient with Wilson disease

Limitations:

Performed with serum ultrafiltrates

Elevated in Wilson disease or other conditions of copper overload

Other tests used to diagnose Wilson disease include serum ceruloplasmin, 24-hour urine copper and hepatic copper

Elevated results should be confirmed with a second specimen to exclude the possibility of external contamination

Follow-up:

Slit lamp examination for Kayser-Fleischer rings and genetic testing may also be helpful

Test name: Ceruloplasmin

ARUP #: 0050160

Methodology: Immunoturbidimetric

Use:

Order to support diagnosis of Wilson disease

Limitations:

Since ceruloplasmin is an acute phase reactant, elevated levels may be found in inflammatory conditions and may not indicate Wilson disease

Pregnancy and oral contraceptives increase ceruloplasmin levels

Low levels of ceruloplasmin are also found in malnutrition, malabsorption, nephrosis and severe liver disease

Follow-up:

Additional Information

Other tests that may assist in the diagnosis of Wilson disease include slit lamp examination for Kayser-Fleisher rings and genetic testing (ATP7B)