Archive for March, 2006


By Rayan Kayssi

A 40 year old woman, recently married and pregnant for the first time, comes to your clinic with a question about the chances of having “a Wilson disease baby”. The woman and her husband are normal and show no signs of the disease.

1. What is the rate of occurrence of Wilson’s disease in the general population? What are some of the common clinical features?

The risk of being affected is the same for both girls and boys.

The frequency of Wilson’s disease is very low: 1 out of 30000 to 50000 births.

In some cases the symptons can be very mild, everyday symptoms such as tiredness, loss of appetite, abdominal pain, vomiting, weight loss, nose bleeds and anaemia.

These symptoms may come and go over a period of months or even years, or they may be more persistent. Some patients also experience kidney problems, i.e. tubular dysfunction, which generally causes no symptoms, and joint problems, which are very rare.

In other cases the symptoms may be more acute, especially when the liver is involved.
Liver disease can be broadly subdivided in to:

• acute liver disease due to copper overload. In this case the patient is likely to be severely ill and yellow.

A liver transplantation may be necessary if treatment does not quickly result in improvement

• acute hepatitis: this is more or less the same as acute liver disease

• chronic liver disease: slow scarring of the liver due to copper overload, which will ultimately also result in severe damage to the liver.
Some of the kinds of neurological problems can include:

• deterioration in school performance or handwriting

• mild tremors

• dystonia: this is a type of cramping or stiffening of the muscles. Often this begins with muscle cramps in the arms or legs, and as the disease progresses, it may result into pulling parts of the body more or less permanently into abnormal postures

• ataxia: loss of the ability to coordinate muscular movement

• muscular rigidity

• dysarthria: this is the medical term for speech abnormality. The dysarthria in Wilson’s disease can take many forms, including slurring, low volume, a repetitive aspect in trying to pronounce certain words, and can progress to complete inability to speak (anarthria).

About one third of patients initially present with psychiatric abnormalities, including depression, personality and mood changes.

2. What genetic events are associated with this disease?

Wilson’s disease is a genetic disorder.

If by accident both partners both carry the same genetic defect, with each pregnancy, there is a one in four chance that the baby will be born with Wilson’s disease.

If the gene is inherited from both mum and dad, like in Wilson’s disease, it is described as being “autosomal recessive”.

3. What pathogenetic mechanisms are responsible for this patient’s symptoms?

The excess copper can build up in the liver and/or brain causing liver damage and/or neurological problems. It can also collect in other parts of the body including the eyes and the kidneys.

Copper begins to accumulate immediately after birth but the symptoms usually appear in the 2nd to 3rd decade.

The first signs are hepatic (liver) in about 40% of cases, neurological (brain) in about 35% of cases and psychiatric, renal (kidney), haematological (blood), or endocrine (glands) in the remainder.

4. What diagnostic procedures would you order to verify the status of the parents and child?

The diagnosis of Wilson’s disease is made by relatively simple tests. These tests can diagnose the disease in both symptomatic patients and people who show no signs of the disease “pre-symptomatic”

The copper accumulation in the eye in Wilson’s disease may cause a diagnostic golden-brown ring to form around the edge of the iris, called a Kayser-Fleischer ring.

This ring is only visible using a special instrument (slit-lamp) and is rarely present before the age of 10 years.

Listed below are the standard laboratory tests used to diagnose Wilson’s disease:

• Urine copper is high; this should be measured in a 24 hour urine collection.

• “Caeruloplasmin”, a copper-containing protein in blood plasma is usually low.

• The copper concentration measured in a liver biopsy specimen will be high.

• The cerebral imaging (MRI) may be abnormal.

• In cases which are difficult to diagnose, copper isotope studies (more complex copper tests) may be performed.
As for the parents:

If you have Wilson’s disease it is very difficult at present to reliably determine whether your partner is a carrier (diagram VII), for which the risk is low, approximately 1:100, or not (diagram VI).

However, as this distinction generally cannot be made, it may be advisable to screen your child for Wilson’s disease, although the chance that this has actually happened is low, i.e. around 1:200 (50% of 1:100).

As the copper build up is slow, reliable biochemical screening can only be done when your child is a few years of age. Repeating this examination might also be necessary, sometimes more than once, as it may be difficult to make a final distinction between carriers (i.e. non-affected) and patients.

5. Without knowing the results of the tests, would can you say to the woman as to the likelihood that her baby will be born with the disease?
I would say that it is usually unlikely for the baby to have Wilson’s disease because there is a slight chance that both of the parents have the gene.

It would require them both to have the gene in order for the baby to have Wilson’s disease.



A 65-year old previously well man presents to the clinic with complaints of fatigue of 3 months duration.

Questioning reveals diffuse weakness and feeling winded when walking uphill or climbing more than one flight of stairs. All of the symptoms have slowly worsened over time.

There are no other complaints, and the review of systems is otherwise negative.

The patient has no significant medical history, social history, or family history.

On physical examination, he appears somewhat pale, with normal vital signs.

The physical examination is unremarkable except for his rectal examination, which reveals brown, guaiac-positive stool (suggests blood in the stool). A blood test reveals anemia.

1. What is the most likely form of anemia in this man? What is the probable underlying cause? Explain your answer.

2. What is the mechanism by which this disorder results in anemia?

3. What might one expect to see in the peripheral blood smear?

4. What other tests might be ordered to confirm the diagnosis?

5. What is the pathophysiologic mechanism of this patient’s fatigue, weakness, and shortness of breath? Why is he pale?


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