Wilson Disease
Metabolic, Biliary Atresia & Related Diseases
Description
Wilson disease is a rare inherited disorder that causes copper to accumulate in your liver, brain and other vital organs. Most people with Wilson disease are diagnosed between the ages of 5 and 35, but it can affect younger and older people, as well.
Copper plays a key role in the development of healthy nerves, bones, collagen and skin. Normally, copper is absorbed from your food, and excess is excreted through a substance produced in your liver (bile). In people with Wilson disease, copper isn’t eliminated properly and instead accumulates, possibly to a life-threatening level. When diagnosed early, Wilson disease is treatable, and many people with the disorder live normal lives.
Wilson disease is present at birth, but signs and symptoms don’t appear until the copper builds up in the brain, liver or other organ. Signs and symptoms vary widely and can include:
- Fatigue, lack of appetite or abdominal pain
- A yellowing of the skin and the whites of the eye (jaundice)
- Golden-brown eye discoloration (Kayser-Fleischer rings)
- Fluid buildup in the legs or abdomen
- Problems with speech, swallowing or physical coordination
- Uncontrolled movements or muscle stiffness
Diagnosis
The diagnosis of Wilson disease can be challenging and doctors rely on a combination of symptoms and test results to make the diagnosis.
These may include:
Blood and urine tests, eye exam, removing a sample of liver tissue for testing (biopsy), genetic testing, or brain MR-imaging.
Management
The goal of medical treatment for Wilson disease is to reduce the damage caused by copper. Treatment is lifelong and may include:
- Copper chelators (D-Penicillamine and Trientine) that pick up the copper and eliminate it in the urine.
- Zinc salts that increase the digestive elimination of copper in the stool.
In severe cases, your doctor might suggest liver transplantation.
Doctors will typically recommend that you limit the amount of copper you consume in your diet and avoid multivitamins that contain copper. You might also want to have your tap water’s copper levels tested. Foods that contain high amounts of copper include: Liver, shellfish, mushrooms, nuts, and chocolate.
Pregnancy and breastfeeding among women with Wilson disease
Conception and contraception in chronic liver diseases in general and specifically in Wilson disease
It is well known that patients with Wilson disease often experience irregular menstrual cycles, such as missed periods, infrequent periods or irregular cycles. This can make conception difficult. Additionally, in non-treated Wilson disease patients miscarriages have been observed. However, this normalises with therapy.
A good copper metabolism and a normalised liver function are the best basic preconditions if you want to become pregnant!
If you have questions concerning genetics or family-screening, you should talk to your gynecologist and take into account a genetic councelling and involve a Wilson expert.
Generally speaking, pregnancies in Wilson disease patients undergoing therapy are normal!
Pregnancy prevention in Wilson disease is possible through hormone-containing (non-copper) intrauterine devices, vaginal rings or the birth control pill, although the use of hormonal contraceptives with a high oestrogen content is not recommended, as these can disturb your liver function tests. If one starts with hormonal contraception (“the pill”) or the preparation is changed, your liver function readings should be checked at short notice.
Problems and dangers for mother and child with chronic liver diseases in general and with Wilson disease in particular
In reference to pregnancy, liver symptoms or severe neurologic symptoms are of particular importance.
In rare cases, Wilson disease patients with decompensated cirrhosis of the liver (i.e. abdominal fluid or jaundice), should be advised against pregnancy.
This should always be discussed with your personal Wilson disease centre since general recommendations are not possible.
After birth, neurological and psychiatric patients in particular may have problems caring for their children. Unfortunately, sometimes a pregnancy also leads to irregular intake of tablets, often for fear of side effects and possible damage to the unborn child. This can have life-threatening consequences for the health of mother and child. Anti-copper drugs must not be stopped during conception, pregnancy or breastfeeding.
Which medicine can be used during pregnancy?
All standard-of-care drugs (namely D-Penicilamine, Trientine and Zinc salts) used to treat Wilson disease can also be used during pregnancy. Discontinuation of the medication is dangerous because the mother’s liver function can deteriorate severely and irreversible neurologic deterioration has been observed.
D-Penicillamine
D-Penicillamine has been in use for a very long time. Therefore, we have the most experience with it during pregnancy, as it was also used in the past for many other illnesses during pregnancy. Both in animal experiments and in humans, it has been described to have adverse effects on fertility, however, in humans – especially in Wilson children – these has not been observed.
→ As a purely precautionary measure and to account for the copper need of the featus, the dose should therefore be reduced to 600-900 mg if possible. In the later trimesters of pregnancy, the main aim is to prevent that a copper deficiency occurs in the child and to avoid wound-healing problems. After delivery, pre-conception doses should be restored.
Trientine
Animal studies have also described fertility-damaging effects when Trientine is taken. These experiments were also carried out with very high doses of the drug and here, too, it is debated whether the resulting low copper levels are not to blame for these malformations. Again, no negative effects have been documented in humans.
→ Under Trientine, the same recommendation as for D-Penicillamine applies in terms of a dose reduction to ideally 2-3 tablets or capsules per day. After delivery, pre-conception doses should be restored.
Zinc
Zinc has not been described to have any adverse effects on fertility in humans.
No dose adjustments are required.
Which medicine should be given during pregnancy?
If you become pregnant while taking D-Penicillamine or Trientine the child will not suffer! Even in pregnant women who do not have Wilson disease, not every child is born healthy.
For pregnancies with zinc, there are also studies that show that pregnancies under this therapy are normal.
In principle, the therapy in progress at the start of the pregnancy should be continued. If you are pregnant, a change of medication should be avoided if possible!
All established therapies are safe for both mother and child!
For a long time, it was discussed among doctors whether, if possible, a woman should switch to zinc before pregnancy. This is certainly not absolutely necessary. However, the principle applies that Wilson disease patients can become pregnant with their therapy if they are well adjusted. They should not necessarily attempt a change in therapy beforehand.
→ Liver function readings should be stable and a steady copper depletion should be achieved; in the initial copper depletion phase, soon after Wilsons´ disease is diagnosed, pregnancy should be avoided as far as possible.
It is important that your therapy is not interrupted during pregnancy!
Pregnancy in advanced liver cirrhosis
If you have a WD-related cirrhosis and large oesophageal varices, pregnancy should be followed in a highly experienced centre. When planning a pregnancy, a planned gastroscopy is advised to see, if there are any varices and how severe they are. The presence of large varices imply significant portal hypertension, which is a consequence of cirrhosis, and might be an additional risk factor for pregnancy outcomes.
In these cases, experts will have to take into account all individual aspects in advising how to proceed and especially which kind of parturition can be adviced for mother´s and child´s best.
Breastfeeding
Breastfeeding under drug therapy with D-Penicillamine, Trientine or zinc is possible in consultation with your doctor!
You should never stop your WD medication for breastfeeding, as medication withdrawal will put you at risk of acute hepatic and neurological deterioration.
As no solid data is available regarding drug passing into the mother´s milk, a risk-benefit evaluation should be taken into account whenever a mother with Wilson disease is willing to breastfeed her child. Generally speaking, doctors are more prone to advise against breastfeeding, despite the fact that some reports have shown normal copper levels in milk under medication. However, a mother always decides for herself whether she wants to breastfeed her child or not.
→ Many mothers with Wilson disease breastfeed without side effects. Nevertheless, D-Penicillamine and Trientine may affect the child and may lead to copper deficiency which can cause disturbances of the child´s blood panel. Thus, this should be checked by the paediatrician, and if this occurs, weaning should be advised.
Summary
• Fertility problems are observed in patients with Wilson disease, mainly among non-controlled or non-diagnosed cases. If your disease is is well controlled with therapy, fertility problems occur much less frequently.
• Pregnancy is possible with all established therapies.
• If your Wilson disease is stable, your liver function is good, and you have no cirrhosis and portal hypertension, no extraordinarily high risks are to be expected in the case of pregnancy.
• Drug therapy must never be interrupted during pregnancy, as this could be a life-threatening risk both for the mother and the child.
• Contact with a Wilson disease experienced centre is recommended, especially during pregnancy.
• Natural breastfeeding is feasible among patients with WD; however, a risk-benefit global assessment should be advisable.
You can download all information regarding pregnancy and breastfeeding among women with Wilson Disease as a leaflet on the right-hand side.
Watch here our video on the patient's perspective in Wilson disease:
Educational Video on Wilson disease: