Genes Matter

Rare diseases, for greater visibility

Rare diseases are more common than we can imagine and a large number of people are affected by this type of diseases globally. In this article, we explain some common characteristics of this type of diseases and the importance of diagnosing them appropriately.

What are rare diseases?  

Rare diseases can be defined as those diseases that have a low prevalence within the population, in other words that affect a limited number of people globally. Each country has its own definition and, therefore, the prevalence at which a disease is considered to be rare may vary; in Europe, a rare disease is one which affects less than 5 in every 10,000 people.

Despite the fact that they affect a limited number of people, large numbers are affected by this type of diseases. According to EURORDIS, over 300 million people worldwide present with a rare disease. Therefore, we could say that a paradox exists between this type of diseases, where the probability of becoming affected by a specific rare disease is low, while the probability of being affected by any of the rare diseases as a whole is high.  To give you an idea, in Spain there are also 3 million people affected by asthma and a little over 5 million suffering from diabetes. As you can see, this means that, as a whole, rare diseases are not as “rare”.

The characteristics of rare diseases

It is estimated that there are between 5,000 and 7,000 rare diseases and, in the majority of cases, these are chronic diseases that involve motor, sensory, neurological, muscular impairments, etc. which affect a person’s quality of life. It is estimated that up to 80% of these diseases are genetic in origin and usually have a complex diagnosis and management where no specific treatment is available.

One of the main characteristics of this type of diseases is that they present a wide range of symptoms, both between the different diseases and between those affected by a single disease, in other words, two people affected by the same disease may present very different clinical signs.

Some examples of rare diseases

  • Neurofibromatosis type 1:

This is a syndrome that affects different parts of the body, in which benign tumours form mainly on the skin and the nervous system. It develops when the NF1 gene is faulty and therefore its protein coding does not function correctly.   

The disease has an autosomal dominant inheritance pattern and although it has 100% gene penetrance, the clinical signs that the affected person presents may be very different, even among those affected within the same family.  

People affected by this disease should conduct regular monitoring of the tumours, as approximately 10% of neurofibromatosis tumours may become malignant. Generally, the treatment is based on controlling the symptoms and it may sometimes include surgery or radiotherapy to remove tumours and/or pharmacological treatment. Early detection and management may improve the quality of life and survival of those affected.  

  • Phenylketonuria:

This is the most frequent congenital error of metabolising amino acids and is usually characterised by mild to serious disability in untreated patients. The cause of the disease is due to anomalies in the enzyme responsible for metabolising the amino acid phenylalanine. This disease follows a recessive autosomal inheritance pattern.

If it is not diagnosed and treated early, the symptoms will appear during the first months of life. These include: delayed development and growth, microcephaly, convulsions, and they may deteriorate giving rise to intellectual disability, behavioural and motor disorders.  

However, if the condition is detected early and appropriate treatment is followed, those affected may avoid the appearance of symptoms and complications.  

  • Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD):

In this disease the enzyme that stabilises red blood cells (erythrocytes) does not function properly. Under certain trigger factors, such as infections, it causes the red blood cells to break down faster than normal when some foods, such as fava beans, are eaten leading to a haemolytic crisis.  

Current treatment is based on avoiding a haemolytic crisis, which means it is aimed at avoiding the triggers that lead to these crises.

The disease follows a recessive autosomal inheritance X-linked pattern and, for this reason, it is more common in men than in women.  

How rare diseases are diagnosed

One of the key problems faced by people affected by a rare disease is diagnosis. The low prevalence of these diseases means that there is less awareness of them which, in turn, results in delayed and poorly defined diagnoses.  

It is estimated that, on average, the diagnosis of a rare disease takes around 4 years, but for 20% of cases, an average of 10 years has been reported. This means that in 31% of cases, the lack of diagnosis causes the deterioration in a sufferer’s health, which could have been avoided with prior specific diagnosis. Furthermore, a delayed diagnosis means that almost 30% of cases of those affected do not receive appropriate management.  

Generally, precise diagnosis is based on a molecular study. The introduction of new methods based on next generation sequencing (NGS), offers a more precise diagnosis of genetic heterogeneous disorders, including cases where a clear hypothesis does not exist for diagnosis. Different studies have shown that sequencing of the genome and/or the whole exome shows great potential for the diagnosis of rare diseases as, in a single sample, it is possible to analyse a very large number of genes as well as being able to provide information on secondary findings and variants of uncertain significance. This is why, today, they are becoming one of the first diagnostic tools, as it is being demonstrated that their use may facilitate the diagnosis of rare diseases.  

Screening for rare diseases

Neonatal screening is one of the most common forms worldwide. In fact, in Spain, the well-known “heel prick test” is carried out on all newborns within 48-72 hours of birth. This mainly screens for between 5 and 20 metabolic diseases, depending on the autonomous community.

At the beginning of 2021, the European Organisation for Rare Diseases (EURORDIS) published a position paper relating to the key principles of neonatal screening in which they indicated that neonatal screening programmes are fundamental for the early identification of a disease. This has many benefits, such as: improving the quality of life for the patient and their family, avoiding the ordeal of diagnosis, the possibility of implementing management to delay the onset of symptoms, etc.

As we have mentioned, many rare diseases are genetic in origin, and most of them appear during childhood. This is why EURORDIS affirms that carrying out screening for diseases during the neonatal period will offer an opportunity to improve the quality of life of all newborns presenting with any of these diseases.  

At Veritas, we support proactive healthcare and preventive medicine, right from the first years of life. That is why we offer neonatal genetic screening to complement the heel prick test in order to detect over 390 diseases, including rare diseases.

Veritas also offers genetic diagnostic services based on genome or whole exome sequencing (myGenomeDx or myExomeDx respectively) for patients with a complex medical history or symptoms that suggest a genetic disease, even when other tests have had negative results. There is also the possibility of extending the test to the trio option (additional progenitor sequencing) in order to identify the molecular cause and to reach a diagnosis.

Do not hesitate to contact us if you would like further information about our genetic tests or our genetic advice services with doctors specialising in genetics.  

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