“Avoid foods with copper at all costs,” the physician said to their new patient.
It’s honest advice if you have a defect in copper metabolism. Patients with Wilson disease (WD) cannot eliminate copper due to a defect in the ATP7B gene and must avoid it in their diet—even watching out for copper in their drinking water. No vegetable juices, no cashews, no baked beans, sweet potatoes, or seafood; and the list goes on.
Read more about the impact of diet on WD.
Yes, I know that for patients with WD, not being able to drink vegetable juice is not high on their list of concerns. But I want to talk about all the different aspects of Wilson disease that impact the quality of life of patients and their families and/or caretakers. They add up.
Avoiding Copper in the Diet and Elsewhere
There are certain meals some patients need to kiss goodbye after receiving their diagnosis. A “copper-conscious diet” it is called. No more shellfish, chocolate (yes, chocolate), nuts, and mushrooms, to name a few. I’m a big fan of these foods so, living without them would leave me feeling pretty gloomy, and these items are only a few on an exhaustive list of foods to avoid.1
I also thought about how this would have affected my wife, who is vegetarian, and it turns out that most of the protein sources in vegetarian diets contain high amounts of copper. So apart from having a truly limited diet, WD patients who wish to follow a vegetarian diet also need to consult a dietician.2
People with WD also must take into account other sources of copper in the environment. For one, if you have copper piping, it may contaminate the tap water. Even without copper piping, it is recommended that households with people with WD request copper level testing in the tap water. The threshold is 100 micrograms per liter.1 You also need to avoid using copper pots when preparing food.
Quality of Life
Quality of life (QoL) is a subjective concept that describes an individual’s overall well-being, taking into consideration various physical and psychological determinants. It is a construct that matters greatly as a measure of outcomes in chronic disease, particularly in disorders that require long-term treatments and have great impairment and impact on daily life. There are several factors that contribute to a decreased QoL, ranging from dietary restrictions to psychiatric comorbidities.
The impact of WD on QoL is an underappreciated topic. Prior to 2021, there were no comprehensive studies on the topic.
A recent systematic review considered 7 papers that used a spectrum of different questionnaires to measure QoL in WD. Research conducted using the 36-Item Short Form Health Survey Questionnaire (SF-36) revealed that one of the major culprits responsible for reducing SF-36 score is neuropsychiatric symptoms.
Read more about the clinical manifestations of WD
One research paper reported that the overall score for patients with neuropsychiatric symptoms was 61 out of a maximum of 100 on the SF-36, compared to 77 for patients with hepatic manifestations. This is consistent with findings from a second publication that reported that patients with neurologic complications have lower scores across all SF-36 dimensions compared to patients with hepatic manifestations. Interestingly, patients treated with penicillamine had significantly higher SF-36 scores compared to those receiving other treatments.
There is a clear pattern emerging that is also backed up by a study using the WHO-QOL-BREF assessment that corroborates these data. In this study, the physical domain of the assessment correlated negatively with neurological symptom score and positively with symptoms of disability. The conclusion is that “more severe disease correlated with greater limitations in physical ability and that longer treatment correlated with better physical ability.”3 The physical domain of the QoL assessment appears to be the area most affected by disease severity and duration, with the psychological, social, and environmental domains minimally affected.4
Impact of Treatment
The mainstays of treatment in WD are copper chelators and zinc salts, which function by removing copper from the blood and impairing normal copper reabsorption, respectively. It is worth noting that these treatments are not always effective and may not be well tolerated.3 Neurologic symptoms may persist in up to half of patients with WD on treatment and up to 10% deteriorate neurologically during treatment.5 Furthermore, adherence is challenging as they must be taken several times a day, each time while fasting.3
Lack of adherence to medication is unsurprisingly a major obstacle to treatment. This is unfortunate since medication adherence is associated with disease improvement in 29.4% and slowed disease progression in 68.3% of patients. It appears that treatment adherence is not influenced by specific medication type, gender, phenotypic presentation, adverse events, or duration of treatment, but rather by education level and a robust family support system.6
How Parents and Siblings Are Affected
QoL has recently gained some well-merited attention; however, we might be forgetting a very important group of people afflicted by this disease—the parents of these patients. Symptoms of WD can appear at any age, with the majority of cases manifesting in childhood to late teenage years, meaning that many patients diagnosed with WD are still in a dependent phase of their lives.
A parent whose child has been diagnosed with WD often won’t know what to expect and is unaware of the challenges that lie ahead for their child and for themselves. Undoubtedly, the sorrow one experiences knowing their child has been diagnosed with an often fatal, rare, genetic disease may be tinged with a sense of guilt. After all, it is a harrowing thought that you may be the source of your child’s affliction. There are studies among parents of children with X-linked diseases that show that X-linked mothers are likely to feel guilty and that X-linked fathers are more likely to blame the mother for the child’s illness.7 For this reason, some families may choose not to test if the disease can be traced back to a single parent.
Some parents prefer to not divulge a child’s genetic condition to preserve happiness during childhood.8 In adulthood, some children will blame their parents for not disclosing their disease earlier or cast blame directly for passing their disease down to them. Additionally, parents of children with WD must consider the fact that the mode of inheritance is autosomal recessive, meaning both parents share genetic responsibility.9
One study highlights some important considerations during the critical moments in which a diagnosis is broken to the family.10 First, the delivery of news has the potential to leave a family feeling like their lives have fallen apart or, if delivered in a clear, sympathetic, and supportive manner, allow the family to receive the diagnosis with a sense of confidence going forward. The family should be in a comfortable environment to receive the news and be allowed to ask all the questions they deem necessary. Additionally, parents should be directed to patient organizations that can provide psychological support if needed. This can help the family feel that they are equipped to deal with the illness.10 Checking in on parents and the family as a whole offers reassurance and is often well received.
Another potential pitfall when disclosing a diagnosis is a lack of information. Information is more accessible than ever before. Parents will almost certainly seek information on the child’s disease, treatment, and prognosis and it’s best to provide this information upfront instead of risking them happening upon potentially harmful false information.
The importance of providing psychological care to parents of children with rare diseases should not be overlooked. They have often been down a diagnostic rabbit hole only to be met with a diagnosis that suddenly impacts every aspect of their lives going forward. But the mental and emotional toll that follows the diagnosis of chronic, incurable disease is shared by the patient, their parents, and any siblings. Siblings may experience a range of contradictory feelings including guilt, pride, worry, and sadness. Furthermore, some siblings may struggle with the attention the diseased child obtains since family life may be centered on providing care for the sick family member.
The fourth pillar of family medicine states that the patient-physician relationship is central to the role of the family physician.11 Whether you are a specialist or a family physician, such as myself, the fourth pillar is central for supporting families with WD. We must have an understanding and appreciation of the human condition, especially the nature of suffering and patients’ response to sickness. So when dealing with WD, remember that this diagnosis confers significant changes that may affect the QoL of the family as a unit. When we provide care for our patients, remember the parents, the siblings, and the caregivers. They are also carrying a burden.
1. Low copper diet for Wilson’s disease. Jackson Siegelbaum Gastroenterology. Published October 29, 2011. Accessed October 18, 2022.
2. Copper conscious eating. Wilson Disease Association. Accessed October 18, 2022.
3. Balijepalli C, Yan K, Gullapalli L, Barakat S, Chevrou-Severac H, Druyts E. Quality of life in Wilson’s disease: a systematic literature review. J Health Econ Outcomes Res. 8(2):105-113. doi:10.36469/jheor.2021.29987
4. Carta M, Mura G, Sorbello O, Farina G, Demelia L. Quality of life and psychiatric symptoms in Wilson’s disease: the relevance of bipolar disorders. Clin Pract Epidemiol Ment Health. 2012;8:102-109. doi:10.2174/1745017901208010102
5. Litwin T, Dzieżyc K, Członkowska A. Wilson disease—treatment perspectives. Ann Transl Med. 2019;7(Suppl 2):S68. doi:10.21037/atm.2018.12.09
6. Masełbas W, Członkowska A, Litwin T, Niewada M. Persistence with treatment for Wilson disease: a retrospective study. BMC Neurol. 2019;19:278. doi:10.1186/s12883-019-1502-4
7. Ca J, Dw H, Na H, Ja W. How does the mode of inheritance of a genetic condition influence families? A study of guilt, blame, stigma, and understanding of inheritance and reproductive risks in families with X-linked and autosomal recessive diseases. Genet Med. 2006;8(4). doi:10.1097/01.gim.0000215177.28010.6e
8. Arribas-Ayllon M, Sarangi S, Clarke A. Managing self-responsibility through other-oriented blame: family accounts of genetic testing. Soc Sci Med. 2008;66(7):1521-1532. doi:10.1016/j.socscimed.2007.12.022
9. Chang IJ, Hahn SH. The genetics of Wilson disease. Handb Clin Neurol. 2017;142:19-34. doi:10.1016/B978-0-444-63625-6.00003-3
10. Kenny T, Bogart K, Freedman A, et al. The importance of psychological support for parents and caregivers of children with a rare disease at diagnosis. Rare Dis Orphan Drugs J. 2022;1(2):7. doi:10.20517/rdodj.2022.0411.
11. Four principles of family medicine. Dalhousie University. Accessed November 14, 2022.