Rare Diseases in Numbers

Rare diseases encompass a broad and heterogeneous group of conditions that individually affect a small number of people, but collectively impact millions worldwide. Despite the low prevalence of each isolated condition, the combined burden on patients, families, and healthcare systems is substantial. 

Understanding what defines a rare disease, how these conditions are classified, and the role of epidemiology in this context is essential to raise awareness, reduce diagnostic delays, and guide public health policies. 

In Brazil, this topic has gained greater visibility in recent years, driven by advances in medical genetics, epidemiology, and the implementation of specific public policies aimed at this group of diseases. 

What is a rare disease and how is it classified?

According to the World Health Organization (WHO) and the Brazilian Ministry of Health, a rare disease is one that affects up to 65 individuals per 100,000 inhabitants. This epidemiology-based definition seeks to standardize care strategies, healthcare network organization, and public health policies. However, this definition is not universal: 

• In the United States, a condition is considered rare when it affects fewer than 200,000 people;
• In the European Union, when its prevalence is lower than 1 in 2,000 individuals.

These differences reflect distinct epidemiological, economic, and social criteria, making international comparisons and policy harmonization more challenging (1-3). 

It is estimated that between 6,000 and 8,000 rare diseases have been described worldwide, most of them of genetic origin. Even so, this is an extremely diverse group from clinical, etiological, and evolutionary perspectives, making classification an ongoing challenge. 

In general, rare diseases can be organized according to different criteria: 

• Origin (genetic or acquired);
• Age of onset;
• Clinical course and affected systems.

In clinical practice and research, they are often grouped into categories such as metabolic, neuromuscular, genetic, autoimmune, infectious, and hematological diseases, which facilitates diagnostic reasoning, clinical management, and the development of specific studies (4-6). 

Tools such as Orphanet and Human Phenotype Ontology (HPO) play a central role in this process by standardizing nomenclature and phenotypic descriptions of rare diseases, enabling the integration of clinical and genetic data on an international scale (4). 

Epidemiology of rare diseases: how to measure what is rare

Epidemiology is the science that studies the distribution and frequency of diseases in populations. In the context of rare diseases, it is essential to quantify their impact, even given their low individual prevalence. 

Its main objectives include estimating prevalence and incidence, identifying regional and demographic patterns, and supporting the development of public health policies. 

However, this field faces important challenges, particularly underreporting and underdiagnosis, as many rare diseases remain without molecular confirmation or are not properly recorded in health information systems. 

This scenario contributes to the so-called “diagnostic odyssey,” characterized by long periods between the onset of initial symptoms and the definition of the underlying cause (7-9). Even with the support of classification systems such as the ICD, Orphanet, and HPO, methodological limitations and the rapid evolution of molecular knowledge require constant updates of these tools (10). 

Rare diseases in numbers: Brazil and the world

Despite their low individual prevalence, it is estimated that approximately 300 million people worldwide live with a rare disease. In Brazil, data suggest that between 10 and 13 million individuals may be affected. 

However, there is an unequal distribution of diagnoses and treatments, with a greater concentration of specialized services in the South and Southeast regions. 

This disparity reflects differences in access to reference centers and genetic testing, reinforcing the need for public policies that promote greater equity in care (7, 11,12). 

Main types of rare diseases: genetic and metabolic

Most rare diseases have a genetic origin, resulting from DNA alterations that may be inherited or arise spontaneously. These conditions can be classified as monogenic, chromosomal, or multifactorial, depending on the underlying mechanism. 

Within this group, rare metabolic diseases stand out, typically associated with defects in enzymes or transporters involved in essential metabolic pathways. Known as inborn errors of metabolism, these conditions may manifest from infancy to adulthood and represent one of the best-characterized groups from both diagnostic and therapeutic perspectives (13-15). 

Accurate identification of these diseases depends on the integration of clinical, biochemical, and genetic data, often supported by advanced technologies such as next-generation sequencing and specialized databases (4, 10). 

Therapeutic advances: who has treatment today?

Over the past decades, the development of therapies for rare diseases has advanced significantly, driven by orphan drug policies and progress in biotechnology, genomics, and gene therapy. 

Even so, it is estimated that only about 5% of rare diseases have an approved medication, with greater concentration in areas such as oncology, neurology, metabolism, and hematology (16, 17). 

In Brazil, access to innovative therapies is broader in certain groups, such as inborn errors of metabolism, cystic fibrosis, and spinal muscular atrophy, particularly when well-established clinical protocols exist and medications have been incorporated into the public health system (SUS). 

Nevertheless, regional inequalities and significant access barriers persist for many other rare conditions (7, 18). 

The role of laboratory innovations in advancing rare diseases

Advances in laboratory techniques have transformed the rare disease landscape, significantly expanding diagnostic capacity and understanding of molecular mechanisms. 

Technologies such as whole genome sequencing, multi-omics approaches, mass spectrometry, and the application of artificial intelligence to genetic data analysis are becoming essential tools in this process (19, 20). 

These methodologies enable the identification of causal genetic variants, interpretation of variants of uncertain significance, discovery of biomarkers, and more precise integration of clinical and laboratory data. 

As a result, they contribute not only to earlier and more accurate diagnoses, but also to the development of increasingly personalized therapies (21, 22). 

Diagnosis: the starting point to transform care

Rare diseases represent a clinical, scientific, and social challenge. Although advances in epidemiology, medical genetics, and diagnostic technologies have been significant, a large proportion of these conditions still lack a definitive molecular diagnosis or specific treatment. 

In this context, investing in high-quality diagnostics is a fundamental step to shorten the diagnostic odyssey, guide therapeutic decisions, support genetic counseling, and improve quality of life for individuals living with rare diseases. 

Expanding access to advanced laboratory testing and integrating clinical and genetic data are now central elements in transforming numbers into effective care. 

What technologies does SYNLAB offer for the investigation of Rare Diseases?

In this scenario, investigating rare diseases requires not only clinical expertise but also access to advanced and integrated diagnostic tools. 

SYNLAB offers a comprehensive portfolio of laboratory tests focused on the genetic and molecular investigation of rare diseases, including technologies such as genomic microarray, NGS (Next-Generation Sequencing) panels, whole exome sequencing, whole genome sequencing, and specific methodologies for mitochondrial DNA analysis, such as sequencing and MLPA. 

These approaches enable the evaluation of chromosomal alterations, single nucleotide variants, deletions, duplications, and structural variants, providing greater diagnostic accuracy even in complex or nonspecific clinical presentations. 

By combining different methodologies within a personalized diagnostic strategy, SYNLAB contributes to shortening the diagnostic odyssey and expanding care possibilities for individuals living with rare diseases. 

Get to Know SYNLAB Group, a Reference in Medical Diagnostic Services!

Performing precise and updated tests is essential for more accurate diagnoses and better treatment guidance. SYNLAB is here to help you. 

We provide diagnostic solutions with strict quality control to the companies, patients, and physicians we serve. We have been in Brazil for over 10 years, operate in 36 countries across three continents, and are leaders in service provision in Europe. 

Contact the SYNLAB team and explore our portfolio. 

Frequently Asked Questions (FAQ)

What is the rarest disease in Brazil?

There is no single “rarest disease” in Brazil. Thousands of rare diseases have been described, many of them with only a few recorded cases in the country or even worldwide. Some conditions affect only a few families. In addition, underreporting and diagnostic challenges mean that many rare conditions remain poorly recognized or not officially registered. 

Is every rare disease genetic?

No. Although most rare diseases have a genetic origin, not all are hereditary. Some rare diseases may be acquired, such as certain autoimmune, infectious, or inflammatory conditions. However, it is estimated that about 70% to 80% of rare diseases have a genetic basis. 

Why does the diagnosis of rare diseases usually take so long?

Diagnosis is often delayed due to the low frequency of these conditions, the wide diversity of symptoms, similarities with more common diseases, and limited access to specialized testing. This journey is known as the “diagnostic odyssey” and can take years before the underlying cause is identified. 

Can genetic tests help even without family history?

Yes. Many rare genetic diseases arise from new (de novo) mutations, without any known family history. Therefore, genetic testing can be essential for diagnosis even when there are no other known cases in the family. 

Do rare diseases have a cure?

Most rare diseases still do not have a definitive cure. However, many can be treated, have their symptoms managed, or show significant improvement in quality of life—especially when diagnosed early. Advances in gene therapies, orphan drugs, and personalized medicine have expanded therapeutic options for certain groups of rare diseases. 

When should I suspect a rare disease?

Suspicion should be considered in cases of persistent, progressive, or unusual symptoms, especially when there is no response to conventional treatments, when there is a suggestive family history, or when multiple organ systems are involved. In such cases, specialized evaluation and genetic testing can be decisive. 

What does epidemiology study in the context of rare diseases?

Epidemiology studies how many people are affected, where these diseases occur, which groups are most impacted, and which genetic, environmental, or infectious factors are involved. Even with small populations, these data are essential to understand the collective impact of rare diseases, guide public policies, organize care networks, and improve access to diagnosis. 

Which test detects a neuromuscular disease?

There is no single test that detects all neuromuscular diseases. Investigation usually involves a combination of clinical evaluation and laboratory and genetic testing. The main tests include genetic sequencing (gene panels, whole exome, or whole genome sequencing), mitochondrial DNA analysis, as well as complementary tests such as muscle enzyme measurements, electromyography, and, in some cases, muscle biopsy. The choice depends on the clinical suspicion. 

References

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17. Miller KL, Fermaglich LJ, Maynard J. Using Four Decades of FDA Orphan Drug Designations to Describe Trends in Rare Disease Drug Development: Substantial Growth Seen in Development of Drugs for Rare Oncologic, Neurologic, and Pediatric-Onset Diseases. Orphanet J Rare Dis. 2021 Jun 9;16(1):265.

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