How does one define “quality of life”? Is it truly measurable? Does translating it into a questionnaire make it more objective? Do patients and caregivers who are asked to fill in “quality of life” questionnaires feel comfortable enough to relate the full breadth of their experience? 

We may never know the answer to these questions, but we must continue to try to understand the one outcome that matters most to patients with rare diseases: the impact on their quality of life. 

Recently, more research has been devoted to understanding the human cost of living with a rare and incurable disease. After all, psychosocial support is as important as physical care. However, in our haste to contribute to the body of medical literature on this issue, we run the risk of being overtly sterile in our attempts to understand the very complex emotional and mental challenges that our patients face. 

Nevertheless, the alternative (ie, inaction) is inexcusable. Hence, researchers and physicians need to work with limited and sometimes flawed data to better understand how we can serve our patients in a holistic manner. 

Hereditary Transthyretin Amyloidosis 

Hereditary transthyretin (hATTR) amyloidosis is the most common type of amyloidosis. Its nomenclature reveals the main feature of the disease: the amyloid deposits of misfolded transthyretin protein produced mainly in the liver. 

“Hereditary ATTR (hATTR) amyloidosis is a progressive, degenerative, and fatal disease,” Yarlas and colleagues wrote in Muscle & Nerve. 

It is a systemic disease that causes amyloid deposit buildup in various organs. In the peripheral nerves, this leads to peripheral neuropathy, often manifesting as paresthesia, hypoesthesia, and neuropathic pain. As the disease progresses, motor systems are affected and patients often lose their ability to ambulate. 

Read more about hATTR amyloidosis etiology

In the heart, amyloid deposit buildups cause restrictive cardiomyopathy, often manifesting as dyspnea, arrhythmia, and heart failure. Multisystem involvement means that patients with hATTR amyloidosis typically also experience gastrointestinal, renal, and ocular problems. 

Existing studies on the impact of hATTR amyloidosis on quality of life heavily suggest it has a net negative effect on patients, especially in terms of physical health. However, the impact of this disease on specific domains of quality of life has not been thoroughly explored; Yarlas and colleagues hence set out to understand more fully the quality of life burden on this patient group. 

The researchers discovered that 2 daily activities that patients with hATTR amyloidosis reported being severely limited to performing due to their disease are engagement in vigorous activities (80%) and climbing several flights of stairs (58%). Patients also reported being limited in engaging with moderate activities (43%) and bending/kneeling/stooping (39%). 

The findings of this study indicate that physical pain/limitation is a serious contributing factor to poorer quality of life. In addition, the findings reveal that the disease results in actual mental burden when appraising mental health parameters in terms of vitality, social functioning, and emotional well-being. 

“This distinction points to the importance of going beyond total and summary scores of [quality of life] measures and looking at scores on particular domains to get a richer profile of patients’ experiences with the disease,” the researchers wrote. 

Broadening the Scope 

In the Orphanet Journal of Rare Diseases, Fuerboeter conducted a brilliant study on the quality of life of pediatric patients with rare diseases during the COVID-19 pandemic. 

At the time of writing, most of the restrictions surrounding the pandemic have been lifted globally (with the exception of China). However, it is worth reflecting on the burden of living with a rare disease, such as hATTR amyloidosis, during a global pandemic. 

“The COVID-19 pandemic and the resulting lockdown measures have been suggested to affect 1.6 billion children, and a recent study found that children, in particular, are affected by the COVID-19 pandemic,” Fuerboeter and colleagues wrote. “Children and adolescents face massive restrictions in their daily lives, including school closures, home confinement, and social distancing rules.” 

How did these restrictions impact the existing challenge of coping with a rare disease? Unsurprisingly, it added an additional, substantial burden on both patients and their families. In terms of quality of life parameters such as emotional and behavioral responses, the mental health of pediatric patients were found to have deteriorated significantly. With regard to their parents, mothers particularly experienced significant mental impairment compared to mothers of children without rare diseases. 

Read more about hATTR amyloidosis treatment

How are we to make sense of the data from this study? One, we must not take for granted the existing disease burden of living or caring for a patient with a rare disease. Second, any additional stressors (such as sudden school closures) can be expected to deteriorate quality of life parameters even further. 

These mental and emotional scars may be invisible, but our empathy need not be. A concerted effort to support struggling patients and their families should be initiated. The silver lining in all of this is that quality of life parameters are dynamic and not static, meaning that improvements in the quality of care can often tip the scales in a more hopeful direction. By putting patients’ mental and emotional needs front and center, we can change outcomes for the better.


Yarlas A, Gertz MA, Dasgupta NR, et al. Burden of hereditary transthyretin amyloidosis on quality of lifeMuscle Nerve. 2019;60(2):169-175. doi:10.1002/mus.26515

Fuerboeter M, Boettcher J, Barkmann C, et al. Quality of life and mental health of children with rare congenital surgical diseases and their parents during the COVID-19 pandemicOrphanet J Rare Dis. 2021;16(1):498. doi:10.1186/s13023-021-02129-0