Low frequency diseases, often called rare diseases, are conditions that affect a small portion of the population. Their limited occurrence presents unique considerations for those impacted and the broader healthcare system. While individually uncommon, these diseases collectively affect millions worldwide.
Understanding What Makes a Disease Rare
A disease qualifies as “low frequency” or “rare” based on specific prevalence thresholds. In the United States, a disease is considered rare if it affects fewer than 200,000 people, approximately 1 in 1,500 individuals, as defined by the Orphan Drug Act of 1983. The European Union defines a rare disease as one affecting fewer than 5 in 10,000 people. These varying definitions highlight the nuanced nature of classifying rarity.
The primary reasons for the rarity of these diseases often involve genetic mutations. Around 80% of rare diseases have a genetic origin, with many being inherited from parents. These genetic disorders can result from a mutation on a single gene (monogenic), mutations on multiple genes (multifactorial inheritance), or structural damage to chromosomes. Huntington’s disease, a neurological disorder, and cystic fibrosis, which affects the respiratory and digestive systems, are examples of rare diseases caused by single gene mutations.
Environmental factors can also play a role in causing rare diseases, sometimes in combination with genetic predispositions. Exposure to certain chemicals, radiation, or even infections can trigger or contribute to the development of these conditions. Mesothelioma, a rare cancer, is linked to asbestos exposure, demonstrating an environmental cause. Some rare conditions, however, still have no clear explanation for their origin.
The Unique Hurdles of Low Frequency Diseases
Individuals with low frequency diseases often face a challenging journey to receive a correct diagnosis, termed the “diagnostic odyssey.” This prolonged process can take an average of 4 to 6 years, involving extensive testing and consultations with numerous specialists. Symptoms of rare diseases can overlap with more common conditions, leading to misdiagnosis or delayed identification.
A significant challenge is the scarcity of medical professionals with specialized expertise. Many healthcare providers may encounter a specific rare disease only once in their careers, making symptom recognition and treatment understanding difficult. This lack of specialized knowledge often results in patients being seen by multiple healthcare professionals across various specialties, who may offer differing opinions or diagnoses.
Research funding for rare diseases is often limited due to small patient populations. Pharmaceutical companies may be reluctant to invest in drug development because of high research costs and the uncertainty of recouping investments from a small market. Consequently, a large majority of rare diseases still lack approved treatments. Developing specialized treatments can also involve significant clinical uncertainty, complicating regulatory approval and demonstrating cost-effectiveness.
Progress in Addressing Rare Conditions
Significant advancements are improving the understanding, diagnosis, and treatment of low frequency diseases. The Orphan Drug Act of 1983 in the United States has incentivized pharmaceutical companies to develop treatments by offering financial benefits like tax credits, grants, and seven-year market exclusivity. This legislation has led to a substantial increase in the number of approved orphan products, with over 1,100 orphan indications receiving FDA approval since its enactment.
International collaboration plays a growing role, bringing together medical specialists and researchers across borders. Organizations like the International Rare Diseases Research Consortium (IRDiRC) unite funding bodies, companies, patient advocacy groups, and scientists to promote global research efforts. The European Reference Networks (ERNs) are virtual networks connecting specialists across Europe, facilitating knowledge exchange for diagnosis and treatment of complex rare diseases.
Emerging technologies are transforming the landscape for rare disease patients. Genomic sequencing allows for the identification of disease-causing mutations in a patient’s DNA, leading to faster and more accurate diagnoses. This advancement supports the promise of precision medicine, which tailors treatments to an individual’s specific genetic makeup. Gene therapies, which aim to replace or repair faulty genes, represent a new avenue for treatment, offering hope for conditions previously without effective interventions.