Focusing on MPS, Professor Susanne Gerit Kircher disucsses how rare diseases are perceived by society.
Mucopolysaccharide storage diseases (MPS) are a group of rare inherited metabolic diseases. Several genes are responsible for producing enzymes, which break down and degrade the glycosaminoglycans (GAGs, the so-called ‘mucopolysaccharides’) in the lysosomes of all cells.
Any gene mutations cause a reduced function of the gene products, the degrading of enzymes, which stops any further degradation process and leads to the storage of any material not degraded in the cells. Impaired function and early cell death result in increasingly enlarging organs.
GAGs are components of many organs and tissues, and any disturbances therefore involve many organs and tissues, including the heart, lung, brain, nervous system, skeleton, and joints, as well as vision and hearing capability. The disease progresses slowly, in most cases from birth onwards, with a chronic disease course and with no hope of recovering.
Depending on the severity of the gene mutations, in some patients there is no enzyme activity at all. These patients have a rapid disease progression which begins early and results in an early death.
In less severe gene variants, there is some residual enzyme activity and symptoms are milder and less life-threatening, but symptoms can also increase over time.
New therapeutic options, such as enzyme replacement therapy for some of the different MPS types (at the moment these are MPS I, II, IVA, VI and VII), are able to transform a severe disease course into an attenuated progression as observed in the attenuated MPS-types.
Early diagnoses and the chance of early haematopoietic stem cell transplantation can also influence disease course substantially and prolong survival dramatically.
Thus, thanks to the ongoing research and improving therapeutic options, the number of patients with MPS reaching adulthood is constantly increasing; and opens new perspectives for affected individuals and their families.
Expectations in disease progression over the years
The first published observations of MPS diseases started exactly hundred years ago by the Scottish medical doctor Charles Hunter (1917) and the Austrian and German paediatricians Meinrad von Pfaundler and Gertrud Hurler (1919).
The patients they described, suffered from severe forms of the disease with early death. The possibilities of symptomatic treatment were reduced and not very effective at influencing the disease progression.
Parents and families were damned to observe a chronic disease progression without any hopes, and a fatal disease outcome was inevitable.
Bone marrow transplantation started in 1980, but earlier interventions with this therapy were often unsuccessful, and the transplant-related morbidity and mortality was high (although the latter was improved with haematopoietic or umbilical stem cell transplantation, which increased the number of surviving patients).
Enzyme replacement therapy began over ten years ago and demonstrated much less adverse effects. Many current MPS patients now receive therapy with weekly infusions of the missing enzymes. These intravenous infusions are also an option if the effect of transplantations decreases over time, or if CNS-involvement is part of the MPS type.
In summary, due to the positive therapeutic effects of causative interventions and much more effective multidisciplinary symptomatic therapies, the survival of affected individuals has improved dramatically. Hand-in-hand, the improved and more feasible diagnostic possibilities reveals an increasing number of MPS patients with more attenuated forms of the disease and with slow disease progression. It is no longer correct to expect a fatal disease course in all patients.
This beneficial positive development opens new questions which demand answers with regard to schools, education, professional life, partnerships, and family life. That means, in principle, we need to explore what needs to be done to enable an adequate quality of a meaningful life, with fulfilled expectations, respect and acceptance by society, and the necessary financial resources.
The challenges of a chronic disease
MPS and many other rare genetic disorders are chronic diseases, slowly progressing and with the need of constant medical care and treatment. Usually, these start during childhood and treatment is necessary for decades; for the entire life of the patient.
From this perspective, rare diseases such as MPS, cystinosis, glycogen storage disorders, or other very common chronic diseases such as diabetes mellitus, atherosclerosis or chronic obstructive pulmonary diseases, do not differ at all.
Patients and families need discipline, patience, treatment compliance, medication adherence, and close co-operation with the healthcare system. The affected have many disadvantages, such as diminished energy, reduced muscular strength and endurance, pains, and physical and psychical handicaps.
But they also suffer from the many prejudices on the part of society and the repeated reproach for needing such expensive therapies.
Even with financial support for care allowance, the personal expenses by/for affected and families are much higher than any financial assistance they receive, and restrictions are thus on everybody’s agenda. The costs of high-priced therapies – if available – cannot be blamed on affected individuals.
The only difference that should be mentioned is that MPS and all the other many thousands of rare inherited disorders are not preventable, whereas many other chronic diseases of today are the result of an unhealthy lifestyle, unbalanced diet, lack of exercise, smoking, and so on, and are therefore essentially preventable.
A lack of respect
MPS patients all have visible handicaps, such as a special physical appearance (“Gestalt”), skeletal deformities, and reduced body size; some also have reduced mobility and use a wheelchair.
The quick reflex-like association of a physical handicap with developmental disabilities is well-known. Often, the affected are not addressed with “Miss”, Mr” or Ms”; communication is often reduced to simple sentences and spoken in a louder voice, or sometimes communication is even directed to any accompanying person.
Many adult MPS patients with small stature are therefore being disrespected as an individual, as they can often be treated as a child and as though they remain ignorant of their disease. One way that this can be addressed is through “transition processing”.
However, the recognition of the transition into adulthood is something that is often spoken about but rarely implemented in a practical way.
Other rare disease patients can suffer in similar ways. For instance, those with an ‘invisible disease’ can often experience prejudice, in that unless symptoms can be seen, they are not seen as having any condition at all. As such, they can fail to be offered adequate assistance or consideration.
Are MPS patients or others with a rare disease really so different?
In the fast-paced modern world, some properties are absolutely necessary: flexibility, mobility, and the ability to adapt to changing technologies and integration, amongst others.
The basic requirement for this is physical, mental and social health. This has been valid for a long time, but it is perhaps not possible for every single person around the world to have god physical, mental and social health.
Indeed, it is more likely that this is true only for a very small minority; the majority of us will experience challenges – ranging from increasing age to adverse environmental conditions or wars – which mean that we risk losing the basic requirements for this.
The reasons might be different, but consequences are the same; few of us are flexible enough, are sufficiently mobile, or are familiar enough with new technologies.
So, what are the differences between those affected with a rare disease such as MPS, or those affected with a chronic disease, and everyone else? It seems that the only difference is that one can see it; that there is the potential to recognise that there is a difference between the individual and the uniform cohort of people.
Yet, if this person is flexible as possible, can work around any physical handicap, is psychically healthy, socially well integrated, and savvy with new technologies, then there is really no difference at all.
The movie Some Like It Hot by Billy Wilder (1959) ends with the very wise sentence “nobody’s perfect”. Let us think more on our own imperfections (currently or in the future) and give those who we think are imperfect different more opportunities.
Ass. Prof Dr Dr Susanne Gerit Kircher
Center of Pathobiochemistry and Genetics
Lysosomal Screening Unit
Medical University of Vienna