Dr. José Hernández-Rodríguez: "Society is not sufficiently prepared to accept people with rare diseases, especially those that cause the highest levels of disability”

In Catalonia, in general the term “malalties minoritàries” (“minority diseases”) has been preferred for years, because we felt that the word “rare” carried a stigma. However, in reality they are the same thing, and in both Spanish and English they are still referred to as “enfermedades raras” and "rare diseases” respectively.

Taking the European context we live in as a point of reference, it is considered that rare diseases affect 5 people in 10,000. Or, in other words, 1 person in 2,000. There are also ultra-rare diseases, which affect even fewer people: 1 person in 50,000, or, in some cases, even 1 person in 1,000,000.

Individually, the figures for each disease vary greatly, but the sum of the total is important: they affect almost 8% of the population. That means that around 30 million people are affected in the European Union. In Spain there are around 3 million, and in Catalonia almost 400,000. Moreover, most of the rare diseases–over 80% of the cases–are genetic in origin.

A very large number: it is estimated that there are over 7,000 rare diseases. Of these, over 4,000 are known to be caused by altered gene expression. However, there are approximately 3,000 for which we still do not know the cause. In fact, there are so many, and some are so uncommon that they are usually grouped into disease families. Even as a specialist, it is impossible to know them all.

Among the best known are metabolic diseases, which are pathologies in which proteins are produced that are altered, or else they are not produced at all. This means that the child does not develop correctly, either physically or cognitively.  They generate dependency from the start and, if not diagnosed and treated quickly, they can end the patient's life or lead to a very high level of disability.  Phenylketonuria is the best known of these diseases.

Rare neurological diseases involve cognitive, motor and/or sensory impairment. Among the many that are known, in adults amyotrophic lateral sclerosis (ALS) stands out.

There are also rare diseases due to malformations from birth, which can remain stable or worsen over the years.  Moreover, there are rare hormonal diseases, linked to the field of endocrinology. And rare cancers and diseases that affect specific organs or systems, such as the liver, the heart, the lungs, the kidneys, the bones, etc.

Finally, I would like to highlight the rare diseases that affect the immune system, which are the ones I deal with.  These include allergic, immune deficiency, autoinflammatory and autoimmune diseases.  

I would say that the most common ones that are make the greatest impact are those that affect the neuropsychological area, because they are detected at a very early age and can be caused by different types of rare disease. The affect the central nervous system directly and mean that the child does not develop properly and also has neurological and cognitive problems. These are the ones the most striking ones, since those who suffer from them not only needs a great deal of health care but also social care. They generate a very high level of dependency and that has a major impact on the patient’s family and work environment.

Society is not sufficiently prepared to accept people with rare diseases, especially those that cause the highest levels of disability. And that creates rejection and it is very frustrating to be rejected whilst you are looking for a solution. Psychologically, it affects the patient and their families a lot.  At present, insufficient resources are available to ensure a decent quality of life for patients with disabling rare diseases and for their families.  In this respect, we still have a long way to go.  There are good intentions because the problem is recognized, but there is a lack of resources.

Detection, diagnosis and research are the three major challenges in rare diseases. In the case of diagnosis, patients with rare diseases are passed from pillar to post before finding out what is wrong with them. Many people go from doctor to doctor for months and years. This pilgrimage is called the "patient journey” and, in cases where it is very long, the "patient odyssey". In theory, detection should be carried out through the primary health care service, by paediatricians, or general practitioners. And, for this reason, professionals should be well trained and prepared to refer the patient to specialized referral centres, regardless of whether they know what is wrong with the patient or not.  

Associations of patients affected by rare diseases constitute a key element that has gradually been consolidated over the last few decades, and can help and guide patients and their families. The two federations that encompass the largest number of these associations, and with which we have a good relationship, are the Catalan Federation of Rare Diseases of Catalonia (Federació Catalana de Malalties Minoritàries de Catalunya, FECAMM) and the  Spanish Federation of Rare Diseases (Federación Española de Enfermedades Raras, FEDER), which operate in Catalonia and Spain, respectively.

Yes, the Hospital Clínic has been a referral centre for many years for rare diseases and, recently, different services and units have received official accreditations that formally endorse them.  Once the patient with a suspected rare disease arrives at a referral centre like ours, the detection process speeds up because we have more experience and high capacity for diagnosis, as well as more means to treat them appropriately, with more up-to-date medication (if they exist, of course). When a patient arrives without a diagnosis, what we usually do is identify the symptoms, compare them with similar ones in conditions we are familiar with and, as far as possible, try to treat the patient with medications like those used for these known diseases.  Likewise, once we diagnose a rare disease in our hospital, we try to monitor the patient for a long time and, if possible, in contact with his/her doctors at their local hospital, to offer the patients and their families the best quality of life.  Sometimes, although it may not seem like much, any improvement means a lot to us.

Firstly, these diseases have to be diagnosed or identified, and grouped together once we know which family they might belong to. And here we come across a major stumbling block, because almost half of rare diseases still remain unidentified or untreated.  In order to improve these aspects, more human, training, structural and research resources are needed. And, if they are ultra rare, the resources allocated to these specific diseases are even scarcer, because the possible advances or solutions only have an impact on very few people.  

In the case of rare diseases, the difficulties facing research is not a matter of the researchers’ interest but rather a purely financial issue, because the companies that develop drugs want a return on their products.  If there is a larger number of potential consumers, the research is speeded up. However, this is not the case for rare diseases, and developing a medication can be a very long, complex and costly task that in the end only reaches very few people. And, for this reason, few laboratories or companies take the risk.

On top of this, there is an administrative deadlock, because many drugs would need to be approved very quickly, and this involves very strict and slow regulatory channels. We have medicines that are known to work, but they have not been approved by the authorities and, therefore, we cannot administer them at the hospital.  When a specialist diagnoses a patient, they often know that there is a drug that can help him/her, but they also know they face an administrative struggle in order to find funding for a non-authorized drug that is usually quite expensive.  In these cases, the hospital has to bear the cost directly and sometimes decides not to do so, normally because of a lack of proven evidence in clinical trials.  And, despite the fact that all this generates a psychological burden and a considerable workload for the professional, in the end it is the patient who pays for it.

Once a professional has identified or oriented the patient’s problem, the question is to know whether there is the will and the capacity to treat it and monitor it in the long term. If all the capacity is not available, which is usually the case with rare diseases in non-tertiary hospitals, the wishes of the professionals at this level should be to refer to patient to expert centres, and to collaborate in the diagnosis and shared monitoring of the patients.  We still lack a great deal of infrastructure dedicated to rare diseases: more hospitals dedicated to them, more financial backing for referral hospitals in the form of more staff and the means to be able to diagnose and treat as many patients as possible.  Of course, a larger budget is also needed for drugs and to authorize those that are useful in real life.  Resources are required to promote research along with the training of more qualified professionals to treat these diseases.

The ERNs are divided up into 24 thematic networks. They were created in 2010 and the Hospital Clínic is currently a member of 11 of these networks. The aim is to ensure knowledge can travel, and not the patients. Complex cases are discussed by doctors from all the European centres in order to increase global knowledge, find specific solutions or studies that can benefit patients. In the future, they will also be used to conduct joint clinical trials with patients all over Europe, to implement a network of patient records and learn more about the characteristics and possible treatments for rare diseases.

In the same way that ERNs are very focused on research, there are two reference centre networks that are active in the area of care. They are the Network of Clinical Expertise Units (Xarxa d’Unitats d’Expertesa Clínica, XUEC), which depends on the Department of Health and operates in Catalonia, and the Ministry of Health’s Referral Centres, Services and Units (Centros Servicios y Unidades de Referencia, CSUR), which treats patients all over Spain. In the XUEC, any patient from any part of Catalonia can be seen and treated in a Catalan referral hospital.  The ones that are treated at the Hospital Clínic are patients with hereditary metabolic diseases, rare kidney diseases, immunodeficiency disorders, autoinflammatory diseases, autoimmune diseases, and rare epilepsies.

On the other hand, the CSUR accreditations are granted to expert centres for conducting specific diagnostic or therapeutic procedures or treating a group of diseases. In the case of the Hospital Clínic, we have services and units accredited as CSUR in hereditary / familial heart diseases, refractory epilepsy, hereditary ataxias and paraplegias, movement disorders, complex pulmonary hypertension, epidermolysis bullosa, hereditary disorders of keratinization, complex glomerular diseases, systemic autoimmune diseases and autoinflammatory diseases.