Wilson’s disease

Published on 05/05/2015 by admin

Filed under Internal Medicine

Last modified 22/04/2025

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118 Wilson’s disease

Instruction

Look at this patient’s eyes.

Salient features

History

• History of consanguinity

• In young adult or child: hepatitis, haemolytic anaemia, portal hypertension or neuropsychiatric abnormalities

• In adolescents: presents as liver disease

• In adults <40 years of age: consider chronic or fulminant hepatitis.

Examination

• Greenish yellow to golden-brown pigmentation at the limbus of the cornea (Kayser–Fleischer ring)

• Look for:

• jaundice (look at the sclera)
• sunflower cataracts
• hepatomegaly
• signs of liver cell failure.

• Look for neurological manifestations: tremor, chorea, mask-like facies with a vacuous smile.

Diagnosis

This patient has a classical Kayser–Fleischer ring with jaundice and hepatomegaly (lesions) caused by Wilson’s disease (aetiology) and does not have a hepatic flap (functional status).

Advanced-level questions

What is Kayser–Fleischer ring?

Deposition of copper in Descemet’s membrane (Fig. 118.1). The ring is most marked at the superior and inferior poles of the cornea. It is often apparent only on slit-lamp examination. It may be absent in patients with only hepatic manifestations, but it is present in those with neuropsychiatric disease.

image

Fig. 118.1 Kayser–Fleischer ring.

(With permission from Goldman L, Ausiello DA 2007.)

Is Kayser–Fleischer ring pathognomonic of Wilson’s disease?

No, it is also seen in primary biliary cirrhosis, chronic active hepatitis with cirrhosis, cryptogenic cirrhosis and long-standing intrahepatic cirrhosis of childhood.

At what age do the neurological manifestations usually manifest?

They usually appear between 12 and 30 years of age. The most frequent first neurological symptom is a difficulty in speaking or writing while in school.

What do you know about the inheritance of the disease?

Autosomal recessive inheritance with the gene ATP7B located on chromosome 13, often associated with a family history of consanguinity. It is caused by mutations encoding a copper-transporting P-type ATPase (Wilson’s disease protein, WNDP). About 27 mutations have been reported; the most common, leading to the substitution H1069Q, is present in about a third of the patients of European extraction.

What do you know about the pathophysiology of this disease?

The precise defect is not known. The major aberration is excessive absorption of copper from the small intestine, with decreased excretion of copper by the liver, resulting in an increase in tissue deposition, particularly in the brain, cornea, liver and kidney. The animal models of this condition are the Long–Evans cinnamon rat and the toxic milk mouse.

What are the biochemical changes in Wilson’s disease?

• Low serum ceruloplasmin level (ceruloplasmin is the copper-carrying protein)

• Serum copper concentration may be high, low or normal

• Orally administered radiolabelled copper is incorporated into ceruloplasmin

• Increased urinary excretion of copper.

How is the diagnosis of a suspected case confirmed?

By the demonstration of one of the following:

• Kayser–Fleischer rings and a serum ceruloplasmin level <20 mg/l

• Serum ceruloplasmin concentration of <200 mg/l and copper concentration in a liver biopsy sample greater than 250 µg/g on a dry weight basis.

How would you treat such a patient?

• Copper-chelating agents:

• Penicillamine, which removes and detoxifies deposits of copper; treatment is lifelong and continuous and is given with pyridoxine to minimize side effects
• Penicillamine should never be given as initial therapy in those with neurological manifestations
• In patients intolerant to penicillamine, trientine dihydrochloride is an acceptable alternative.

• Zinc salts

• Tetrathiomolybdate with zinc salts: treatment of choice in those with neurological symptoms.

What are the clinical stages of Wilson’s disease?

Wilson’s disease progresses through four clinical stages.

1 Asymptomatic accumulation of copper in the liver, which begins when the patient is born.

2 Patient is either asymptomatic or manifests with haemolytic anaemia or liver failure.

3 Copper accumulates in the brain.

4 Progressive neurological disease.

What are the radiographic features of Wilson’s disease?

• Osteopenia: most apparent in the hands, feet, and spine

• Arthropathy

• Articular abnormalities: subchondral bone fragmentation, cyst formation and cortical irregularities, most commonly identified in the wrist, hand, foot, hip, shoulder, elbow and knee. Irregularity and indistinctness of the subchondral bone may form a characteristic ‘paintbrush’ appearance (Fig. 118.2)

• Osteomalacia and rickets have been reported. Radiologic signs of rickets, retardation of skeletal maturation and pseudofractures may be observed

• Additional characteristic radiographic findings are small, distinctly corticated ossicles around the affected joint and periosteal bone formation at the attachment sites of tendons and ligaments

• Chondrocalcinosis is rare, usually limited to the knees

image

Fig. 118.2 Brushlike calcifications (arrow) along the articular surface.

(With permission from Firestein et al. 2008.)

Samuel Alexander Kinnier Wilson (1877–1937) qualified in Edinburgh and worked at the National Hospital, Queen Square, London, as a neurologist (Wilson SAK. Progressive lenticular degeneration. A familial nervous disease associated with cirrhosis. Brain 1912;34:295).

Bernard Kayser (1869–1954) and Bruno Fleischer, both German ophthalmologists, described the same condition in 1902 and 1903 respectively.

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