Rare Disease Day lands on the last day of February every year and aims to raise awareness of rare diseases amongst the general public, researchers, and decision makers. It began in 2008, where initially events took place in just 18 countries [1]. Last year events were held in over 100 countries, showing the important progress an awareness day can bring.
The European Union’s definition of a rare disease is one that affects fewer than 1 in 2,000 people [2]. Although each disease is uncommon there are over 7,000 rare diseases so they collectively affect around 350 million people worldwide. This is more than all the people living in America, the 3rd most populous country in the world [3]. There is a variety in the prevalence of rare diseases, with Duchenne muscular dystrophy (DMD) being one of the most common, affecting 2,500 people in the UK, while others, such as Wolfram syndrome, affect just 100 people in the UK. Many syndromes without a name (known as SWAN) are only known in a single person [3]. Rare diseases can be both life-limiting and life-threatening, and they disproportionately affect children [4].
70-80% of rare diseases are genetic, which are usually inherited. They can be recessive or dominant traits, autosomal or sex-linked (either on the X or Y chromosome), and they can also be caused by alterations in mitochondrial genes [3,5,6]. Let’s explain what that means. Each person has two genes which code for the same protein, called alleles, and will inherit one from their mother, and one from their father. If there is a mutation in a gene it can cause a disease. Two examples of an autosomal recessive rare diseases include cystic fibrosis, and phenylketonuria [7,8]. A person will only have an autosomal recessive disorder if they have two faulty alleles which cause the disease. This means that each parent must have at least one mutated allele for their child to have the disease [6]. In autosomal dominant rare diseases such as Huntington’s disease and progeria, only one mutated copy of the allele is necessary for a person to be affected [9,10]. In some cases, an affected person inherits the mutated allele from an affected parent. In others, the condition may result from a new mutation in the gene and occur in people with no history of the disorder in their family [6]. X-linked recessive diseases include haemophilia A and DMD [11,12]. These diseases primarily affect males because they only have one X chromosome and so one faulty gene in their X chromosome will cause the disease [6]. X-linked dominant diseases include Goltz syndrome and as it is dominant it will affect females even if only one of their X chromosomes contains the mutated gene [6,13]. Y-linked diseases are extremely rare and can only affect males because females do not have a Y chromosome [6]. Mitochondrial diseases include maternally inherited diabetes and deafness (MIDD) and are caused by mutations in mitochondrial DNA [14]. Only females can pass on mitochondrial mutations to their children as only egg cells contribute mitochondria to the embryo, but both males and females can be affected [6].
The other 20-30% of rare diseases are caused by bacterial or viral infections, allergies and environmental causes, or are degenerative and proliferative [5]. Examples include anthrax, an infectious disease caused by bacteria, and hypoplastic left heart syndrome (HLHS) which is a rare congenital heart defect where the left ventricle of the heart does not develop properly and is less able to pump blood around the body [15,16]. Acromegaly is an acquired rare disease which occurs in adulthood when too much growth hormone is produced, and it is usually caused by the growth of a benign pituitary gland tumour [17]. Another example is elephantiasis, a disease where obstruction of the lymph vessels leads to major swelling of limbs, which is usually caused by a parasitic infection [18].
In the UK around 3.5 million people are affected by a rare disease, which is about 1 in 17 people [19]. Despite the scale of the issue, a significant proportion of these patients do not have access to the right care and treatment [20].
The UK Rare Diseases Framework was set up by the Government in 2013 to tackle these problems and it established the following four priorities in order to improve the lives of people living with rare diseases [4]:
- Priority 1: helping patients get a final diagnosis faster
- Priority 2: increasing awareness of rare diseases among healthcare professionals
- Priority 3: better coordination of care
- Priority 4: improving access to specialist care, treatments, and drugs
Current scientific knowledge and technology is making diagnoses and treatment possible for patients that was unimaginable a few years ago [21]. One of the major advances that has been made is through the UK 100,000 Genomes Project, which sequenced genomes from NHS patients with rare diseases or cancer, and it has helped 1 in 4 patients with an undiagnosed rare disease receive a diagnosis for the first time [4].
Pharmaceutical companies may be less inclined to develop therapies for a rare disease, as there is a smaller drug market, so drugs produced for rare diseases are therefore coined ‘orphan medicines’ [22,23]. To combat this, some countries have offered incentives to increase the number of drugs manufactured for rare diseases [23]. In fact, in Scotland, access to new medicines for rare diseases has significantly increased through a new ultra-orphan medicines pathway. This scheme was introduced in October 2018 and ensures faster access to new treatment for people living with rare diseases [4].
Unlike other diseases, rare diseases do not have doctors specialising in individual diseases. It is therefore essential that awareness for rare diseases is increased and that they are more regularly considered in diagnoses. Although individually these diseases may not affect very many people, they have a huge impact on those afflicted, and cumulatively they affect millions. Increasing awareness of rare diseases will hopefully help the rare disease community and mark the way for positive change.
Ella White
Bibliography:
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