What are rare diseases?

The Rare diseases ( ER ) Are a pathological condition that affects a very small group or number of people compared to other diseases more prevalent in the general population (Richter et al., 2015).

In the case of Europe, rare diseases affect approximately one person for every 2,000 citizens of the general population (Spanish Federation of Rare Diseases, 2016).

However, in the case of the United States, a disease is considered to be rare or rare when it affects approximately 200,000 people at a specific time (Rare Disease Day, 2016).

The main feature of rare diseases, also called orphan diseases, is the wide variety of symptoms that may appear. A particular pathology can produce very specific and very different symptoms of any other rare disease. In addition, both the symptoms and the clinical course are also very heterogeneous among patients suffering from the same pathology (Rare Diseases Europe, 2007).

A very large number of rare genetic diseases have been reported in children and adults worldwide. At present, between 5,000 and 8,000 different pathologies are known and in addition, new rare diseases are frequently documented in the medical literature (Richter et al., 2015).

In general, this type of pathologies are the product of alterations or genetic mutations. However, they can also develop as a consequence of the presence of infectious, immunological, viral and / or degenerative pathologies (Cortés, 2015).

What is a rare disease?

The general definitions of the concept of disease refer to a deterioration of health (physical or mental) or an abnormal condition in the functioning of the person (European Organization for Rare Diseases, 2005).

Rare diseases, therefore, are pathologies that occur with a very low incidence in the general population, are considered to be uncommon (COFCO, 2016).

In spite of this, the World Health Organization , Notes that there are a large number of people affected by these diseases. Different studies have estimated that these can affect approximately 7% of the population (COFCO, 2016).

There are thousands of rare diseases that have been described (World Health Organization, 2012). These include Duchenne muscular dystrophy , the cystic fibrosis , the hemophilia or the Angelman's Syndrome .

Who suffer from rare diseases?

Depending on the country there are different statistical criteria to consider a pathology as belonging to the group of rare or infrequent diseases.

Despite this, some research projects estimate that there are more than 300 million people in the world affected by a rare disease (Cortés, 2015).

In the European population, it has been estimated that there are between 6,000 and 8,000 types of rare diseases that affect approximately 6-8% of the population (European Organization for Rare Diseases, 2005).

As a result of these figures, it is probable that about 3 million people living in Spain, 27 million people living in Europe, 42 million people living in Latin America and 25 million people living in North America, may suffer from some of the diseases Rare (Spanish Federation of Rare Diseases, 2016).

With regard to age, it has been observed that 75% of cases of rare diseases affect children. In particular, it has been documented that 30% of children with rare diseases die before 5 years of age (European Organization for Rare Diseases, 2005).

Despite this, there is a high percentage of rare diseases that appear in adulthood, such as Huntington's disease wave Crohn's disease (COFCO, 2016).

What are the characteristics of rare diseases?

There is a very wide and heterogeneous variety of disorders and specific symptomatology. In addition, a great deal of common symptomatology?? Can obscure or make difficult the diagnosis of a rare disease (Rare Disease Day, 2016).

In spite of symptomatic heterogeneity, rare diseases are considered serious pathologies, with a progressive and chronic clinical course (Orphanet, 2012) that are going to produce different physical, cognitive, sensorial and / or behavioral alterations (Spanish Federation of Rare Diseases, 2016).

In some types ( muscular atrophy , Rett syndrome , Among others), signs and symptoms appear from the birth or early stages of the person's life (Orphanet, 2012).

Briefly, the Spanish Federation of Rare Diseases (2016) highlights some of the most significant features of rare diseases:

• Early appearance . Approximately 2 of every 3 children begin to develop the symptoms characteristic of the pathology that suffers before the 2 years of age.
• A lot of people are going to present themselves Chronic pain Derived generally of the physical and sensorial alterations.
• Presence of motor deficits , Sensory, cognitive in approximately 50% of the cases.
• Presence of functional dependence In 1 out of 3 cases.
• Reduction of life expectancy In most cases. About 10% of individuals die between 1-5 years, while another 12% die between 5-15 years of age.

What are the causes of rare diseases?

The specific cause of many rare diseases remains in question. Despite this, many types occur as a result of genetic alterations, called"rare genetic diseases". (National Human Genome Research Institute, 2012).

When a genetic mutation exists, this can be transmitted to the offspring, due to this there are several cases of rare hereditary genetic diseases (National Human Genome Research Institute, 2012).

Some examples of rare diseases caused by genetic factors are: cystic fibrosis , Huntington's disease , Muscular dystrophies (National Human Genome Research Institute, 2012).

On the other hand, we must take into account that there are other types of factors that may precipitate the appearance of a rare pathology.

On the one hand, there are pathological factors that can directly cause the development of a rare disease: viruses, bacteria, immunological processes, etc. (National Human Genome Research Institute, 2012).

On the other hand, some environmental factors that appear to show a secondary modulating influence have also been described: dietary habits, consumption of substances such as tobacco or alcohol, exposure to chemicals, etc. (National Human Genome Research Institute, 2012).

For example, most of the Mesothelioma (Pathology affecting cells lining the chest cavity) are due to exposure to asbestos (National Human Genome Research Institute, 2012).

How many types of rare diseases are there?

Rare or rare diseases can develop due to a wide variety of factors, therefore, a very wide variety of types have been described.

In addition, the same pathology can be presented with different clinical manifestations between people or different subtypes can be described within the same disease (Cortés, 2015).

There are currently 6,000 to 8,000 rare disease types reported, and this number continues to increase steadily as a result of clinical and experimental documentation.

In general, all rare pathologies affect the physical, cognitive habilyties , Behavioral spectrum, and sensory skills (Cortés, 2015).

Despite the fact that these are diseases that have a reduced incidence at the population level, there are some subtypes that occur more frequently than others.

Some of the most common types?? Of rare diseases are (Cortés, 2015):

• Achondroplasia : This is a pathology that presents with a frequency of 1: 25,000. The main cause is a mutation of the FGR3 gene. This type of pathology can produce macrocephaly, facial hypoplasia, reduction of stature, among others.
• Angelman's Syndrome : The frequency of this syndrome has been estimated at 1: 15,000. The mutation of the UBE3A gene has been related to the appearance of this pathology and the associated symptoms: mental retardation, microcephaly, absence of language, electroencephalography alterations, ataxia, etc.
• Bardet's syndrome Biedl : This type of pathology has a frequency of 1: 125,000 and the mutation of the BBS1 gene has been related to its occurrence. The following conditions are frequently present: mental retardation, obesity, retinitis, polydactyly or hypogynadism.
• Tuberous sclerosis : This is a pathology that occurs at a frequency of 1: 6,000 and has been linked to the mutation of the TSC1 / TSC2 genes. People who have it often present: seizures, renal cysts, hypochromas, subcutaneous nodules, angiofibromas and cardiac rhabdomyomas.
• Phenylketonuria : Is a disorder that has a frequency of 1: 10,000 and occurs as a consequence of a mutation of the PHA gene. Some of the symptoms that develop as a result of their suffering are: mental retardation, microcephaly, behavioral disorders, seizures and / or hypopigmentation of the skin.
• Cystic fibrosis : It is a pathology that occurs with an approximate frequency of 1: 10,000 and is related to the mutation of the CFTR gene. The associated symptomatology is characterized by: chronic lung infections, pancreatic insufficiency, brochiectasis and infertility in men.
• Neurofibromatosis type 1 : Is a pathology that has a frequency of 1: 3,000 and is related to the mutation of the NF1 gene. The associated symptoms are as follows: gliomas, sphenoid dysplasia, Lisch's nodules and mánchas / freckles on the skin.
• Prader Willi Syndrome : It is a syndrome that presents with a frequency of 1: 25,000 and that is related to a variety of genetic factors, specifically with alterations in the genetic ones in: 15q11.6 (SNRRN, MAGEL2, NDN, OCA2, SNORD115 , SNORD116). The clinical spectrum of Prader Willi syndrome may include: behavioral alterations, hypogonadism, hyperphagia, obesity, facial dysmorphia, and neonatal hypotonia.
• Rett syndrome : This type of syndrome occurs with a frequency of 1: 12,000 in women and is related to a mutation in the MECP2 gene. The associated symptomatology comprises: Sleep disorder , Autistic behaviors, steroids in the upper extremities, scoliosis , Hyperventilation , Bruxism , Microcephaly I Mental retardation progressive.
• Sotos Syndrome : This pathology presents with a frequency of 1: 50,000 and has been related to alterations in the NDS1 gene. Some of the associated symptoms are: learning difficulties, macrocephaly, magalencephaly, increase in the size of the feet and hands, coordination disorders, among others.
• Williams syndrome : It is a pathology that presents a frequency of 1: 8,000 and has been related to a wide variety of genetic factors: genetic alterations in 7q11.1 (ELN, BAZ1B, CLIP2, GTF2, GTF2URD1, LIMK1, RFC2, TBL2 ). The symptomatology that presents as a consequence of the suffering of this syndrome includes: Hypercalcemia , Hyperacusis , Supravalvular aortic stenosis , Peripheral pulmonary stenosis , Behavioral alterations and visuomotor skills disorders.

Is there treatment for rare diseases?

The treatment will depend fundamentally on the type of pathology that the person presents. In some cases, therapeutic interventions are used to treat symptoms, both to control the progression of the disease and to improve overall quality of life.

Despite this, clinical trials and the various investigations that are underway seek to clarify the biological bases of each of the rare disease types and thus find a cure for many of the pathologies that have a mortality prognosis in Early stages of life.

What are the main problems with people with rare diseases and their relatives?

Until relatively recently there was a great ignorance about the rare diseases, hardly any studies and clinical investigations existed.

Although there has been a considerable increase in the volume of information on some of the most common rare diseases, a large number of scientific and conceptual gaps remain.

The most common problems are the determination of the diagnosis, the search for specific and adequate information about a particular pathology or the difficulty of finding specialized professionals (Orphanet, 2012).

People with rare diseases and their families will find significant difficulties in accessing quality health care or social and medical support (Orphanet, 2012).

Those affected by this type of pathology present an increased vulnerability in the psychological, social, economic and cultural areas, mainly due to the lack of specific medical protocols or a lack of specific and appropriate social policies (Orphanet, 2012).

CONCLUSIONS

Although rare diseases are rare or uncommon pathologies, there are now a large number of people affected by them.

An individual suffering from a particular type of rare disease may present major problems and deficits at the physical, sensory and cognitive levels and is therefore likely to have a significant degree of functional disability.

Due to the uncommon nature of these pathologies, state policies usually allocate few economic resources for both clinical and experimental research and the development of specialized medical care.

Because of these circumstances, in most cases the pathologies are not diagnosed in time or the symptoms and syndromes are not identified efficiently so that erroneous or confusing diagnoses are made. As a consequence of this, the therapeutic intervention is not adequate, worsening both the severity and the course of the disease and the prognosis.

It is essential to increase knowledge about this type of pathologies and, therefore, the resources allocated to them. Early diagnosis and intervention to improve the quality of life of people with rare diseases is essential.

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