ACREDA Journal

Rare diseases are medical conditions affecting a small fraction of the population, typically fewer than 1 in 2,000 people in Europe and fewer than 200,000 individuals in the United States. Ultra-rare diseases are an even smaller subset, often affecting fewer than 1 in 50,000 people. These conditions are frequently genetic, chronic, and debilitating, with many manifesting in early childhood.

While rare diseases are increasingly recognized and researched in high-income countries, they remain largely unrecognized, underdiagnosed, and untreated in LMICs. The lack of proper surveillance, diagnostic tools, and awareness among healthcare professionals contributes to this gap. Consequently, millions of people in LMICs suffer without an accurate diagnosis or appropriate treatment, often leading to severe disability or premature death.
 

Why Rare and Ultra-Rare Diseases Are Unrecognized and Under-Diagnosed in LMICs

There are several interconnected reasons why rare and ultra-rare diseases are often overlooked in LMICs:

1. Limited Diagnostic Capacity

Most rare diseases require advanced diagnostic tools such as genetic sequencing, biochemical assays, and specialized imaging techniques—resources that are often scarce in LMICs. Many healthcare facilities in these regions lack access to:

• Genetic Testing: Next-generation sequencing (NGS), whole exome sequencing (WES), and chromosomal microarray analysis are rarely available.
• Biochemical and Enzyme Assays: Many rare metabolic disorders can be identified through enzymatic and biochemical tests, but these are often unavailable.
• Newborn Screening Programs: Essential for early detection of metabolic and genetic disorders, but coverage remains extremely low in LMICs.

2. Overlapping Symptoms with Common Diseases

Many rare diseases mimic more prevalent conditions such as malnutrition, infectious diseases, and neurological disorders. For example:

• Lysosomal storage diseases (e.g., Gaucher disease, Fabry disease) may be misdiagnosed as malaria, tuberculosis, or malnutrition.
• Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are often mistaken for cerebral palsy.
• Congenital adrenal hyperplasia (CAH) may be confused with delayed puberty or PCOS in adolescent girls.

3. Lack of Awareness Among Healthcare Professionals

In many LMICs, medical education and training do not prioritize rare diseases. Physicians and healthcare workers are more likely to focus on conditions with high morbidity and mortality rates, such as malaria, tuberculosis, HIV/AIDS, and malnutrition. As a result, rare disease cases may not be identified due to a lack of knowledge and suspicion.

4. Inadequate Data Collection and Surveillance

Most LMICs do not have rare disease registries, making it difficult to track prevalence, diagnosis rates, and treatment outcomes. Without reliable epidemiological data, governments and healthcare organizations struggle to allocate resources for research, diagnostics, and treatment.

5. Financial and Infrastructure Constraints

Rare diseases are often expensive to diagnose and manage, requiring long-term medical care, specialized treatment, and orphan drugs. Many LMICs have weak healthcare financing systems, making it difficult for patients to access costly diagnostic tests and therapies.

6. Cultural and Social Factors

• In some communities, rare diseases may be attributed to supernatural causes, leading to stigma and delayed medical intervention.
• Some genetic conditions are more common in regions with high rates of consanguinity (e.g., Middle East, South Asia, parts of Africa), yet genetic counseling remains underdeveloped.
• Many families may not seek medical care due to fear of discrimination or economic constraints.
   

Strategies for Addressing Unrecognized and Under-Diagnosed Rare Diseases in LMICs

Given these challenges, a multifaceted approach is needed to improve diagnosis, surveillance, and treatment of rare and ultra-rare diseases in LMICs.

1. Expanding Access to Diagnostic Tools

• Low-Cost Genetic Testing: Emerging technologies, such as nanopore sequencing and portable PCR devices, offer cost-effective genetic testing solutions.
• Regional Diagnostic Hubs: Establishing centralized facilities for genetic testing can serve multiple countries and reduce costs.
• Newborn Screening Expansion: Implementing cost-effective screening methods (e.g., tandem mass spectrometry for metabolic disorders) in neonatal care programs.

2. Enhancing Medical Education and Awareness

• Training for Healthcare Providers: Developing online and in-person training modules on rare diseases for doctors, nurses, and community health workers.
• Integration into Medical Curricula: Introducing rare disease education in medical and nursing schools.
• Telemedicine and AI-Assisted Diagnosis: Using AI-powered platforms to help physicians recognize potential rare disease cases based on symptoms and medical history.

3. Strengthening Data Collection and Surveillance

• Establishing National and Regional Rare Disease Registries: Collecting epidemiological data to track disease burden and inform policy decisions.
• Partnerships with International Research Networks: LMICs can collaborate with global initiatives like Orphanet, the Global Commission on Rare Diseases, and patient advocacy groups to share data and resources.

4. Policy and Health System Strengthening

• Orphan Drug Legislation: Encouraging local pharmaceutical companies to develop and manufacture treatments for rare diseases.
• Public-Private Partnerships (PPPs): Collaborating with global biotech firms, non-profits, and universities to fund research and drug accessibility programs.
• National Rare Disease Policies: LMICs should adopt rare disease policies similar to those in high-income countries, including coverage for orphan drugs and diagnostic support.

5. Leveraging Digital Health and AI

• AI-Powered Diagnostic Tools: Smartphone apps and machine learning models can assist in diagnosing rare diseases based on images and patient-reported symptoms.
• Telehealth Networks: Allow specialists in high-income countries to provide virtual consultations to physicians in LMICs.

Practical and Proven Solutions: Global and Regional Examples

Several successful initiatives demonstrate that addressing rare diseases in LMICs is possible:

1. India’s Rare Disease Policy (2021)

India has launched a rare disease policy that includes government funding for treatments, expanded newborn screening, and subsidies for genetic testing. This model can be adapted in other LMICs.

2. Genomic Sequencing in Africa

The Human Heredity and Health in Africa (H3Africa) initiative has established genomic sequencing centers across Africa, enabling research on genetic disorders and rare diseases.

3. Newborn Screening in Brazil

Brazil has implemented nationwide newborn screening programs for conditions like phenylketonuria (PKU) and sickle cell disease, demonstrating the feasibility of cost-effective screening in an LMIC.

4. Rwanda’s Digital Health Innovations

Rwanda has incorporated AI-driven diagnostics into its healthcare system, improving the identification of neurological and metabolic disorders in children.

5. Bangladesh’s Genetic Counseling Program

With support from international NGOs, Bangladesh has launched genetic counseling services to reduce the burden of inherited rare diseases in high-consanguinity populations.

Conclusion: Moving Forward with Sustainable Solutions

Addressing rare and ultra-rare diseases in LMICs requires a holistic approach combining policy reform, expanded diagnostic capabilities, medical education, international collaboration, and innovative technology. By leveraging AI, digital health tools, and cost-effective screening programs, LMICs can significantly improve the recognition and management of these conditions.

The success of initiatives in India, Africa, Brazil, and Bangladesh shows that even resource-constrained settings can develop effective strategies for rare disease diagnosis and care. The key lies in multisectoral collaboration, strong policy frameworks, and a commitment to integrating rare diseases into national healthcare priorities.

Investing in rare disease research and diagnostics in LMICs is not just a medical necessity but a global health imperative—ensuring that no patient, regardless of geography, is left without hope.