Raising Global Awareness for Rare Diseases on Rare Disease Day

What is a rare disease?

In the United States, a rare disease is defined as a condition that affects fewer than 200,000 people in the US. Rare diseases became known as orphan diseases because drug companies were not interested in adopting them to develop treatments. The Orphan Drug Act created financial incentives to encourage companies to develop new drugs for rare diseases. Different countries have their own official definitions of a rare disease. In the European Union, a disease is defined as rare when it affects fewer than 1 in 2,000 people. Rare diseases include Naxos disease, Rippling muscle disease, Caffey disease, Gaucher disease, Pompe disease, mucopolysaccharidosis, tuberous sclerosis and so forth. Most rare diseases are chronic serious diseases, usually life-threatening.

What causes rare diseases?

The majority of rare diseases are thought to be genetic, directly caused by changes in chromosomes or genes. However, many rare diseases, including infections, some rare cancers, and some autoimmune diseases, are not inherited. However, the exact cause of many rare diseases is still unknown. Currently, about 7,000 diseases caused by the alteration of specific genes are known, and 1 in every 100 babies suffers from one. Since rare diseases often are difficult to diagnose, it can take years to obtain an accurate diagnosis. Even after a proper diagnosis, treatment often is unavailable. Only about 5% of rare diseases have a treatment approved by the FDA.

Diagnosis and genetic testing of rare diseases

Genetic testing technology is an important method to clearly diagnose rare diseases. Variations at different levels of chromosomes, genes, and bases can cause disease. Classical gene detection methods include chromosome karyotype analysis, fluorescence in situ hybridization (FISH), microarray comparative genomic hybridization (aCGH), multiple ligation dependent probe amplification (MLPA), etc. New emerging technologies such as second-generation sequencing and third-generation sequencing technologies provide powerful tools for rare disease diagnosis.

Rare disease diagnosis/screening market

From the perspective of clinical demand, the rigid demand market for rare disease and genetic disease diagnosis can be divided into the following two major segments:

• For patients with current symptoms, a diagnosis is needed for effective treatment
• For families of patients, they often want to regenerate a healthy child. At this time, in vitro fertilization (IVF) is often needed. Out of the need for fertility guidance, three markets will be derived: carrier screening, preimplantation screening, and prenatal diagnosis

Current Problems in Rare Disease Diagnosis

1. The diversity of rare disease pathogens

Although more and more disease-causing genes have been revealed, many of them are still unknown. Therefore, there is a certain controversy regarding the direction of genetic testing. There is still uncertainty in diagnosis based merely on genetic testing results. Auxiliary tests are necessary such as imaging, electrophysiological examination, blood biochemical testing and so on.

2. Gene Testing Fees

Gene sequencing methods for rare diseases are frequently used and the overall cost is relatively high. Besides, the structure of the disease-causing gene, the type of mutation detected, and the number of exons in each gene and the number of disease-causing genes that need to be detected for a clinical phenotype is also different. This makes gene sequencing not as a universal project as other projects, and it can be widely carried out.

3. Ethical Issues of Gene Testing for Rare Diseases

From the point of view of testing, the diagnosis of rare diseases is mostly prenatal testing. At this time, the closer the type of specimen to the baby is, the higher the theoretical accuracy, but this involves the problem of sampling risk, and it is also common to cause medical disputes.

For Research Use Only.