Orphanet Journal of Rare Diseases | Dried Blood Spot Testing Facilitates the Development of a Rare Disease Diagnostic Network in Africa

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This study evaluates the diagnostic feasibility of dried blood spot (DBS) technology across multiple African countries through multinational collaboration, highlighting the critical roles of training and sample transportation, providing a practical model for rare disease diagnosis and treatment in low-resource settings.

 

Literature Overview

The article 'Improving access to rare disease diagnostics in Africa: insights from a multinational pilot study,' published in the Orphanet Journal of Rare Diseases, reviews and summarizes a pilot study on rare disease diagnosis conducted across eight sub-Saharan African countries. Initiated jointly by FYMCA Medical Ltd., the International Gaucher Alliance (IGA), and the Centre for Human Metabolomics (CHM) at North-West University in South Africa, the study aims to evaluate the feasibility of large-scale screening for lysosomal storage disorders (LSDs) using dried blood spot (DBS) technology, while enhancing local clinicians’ ability to recognize rare diseases. By organizing clinical training, establishing cross-border sample transportation mechanisms, and centralizing 6-plex LSD testing in South Africa, the study systematically analyzed diagnostic efficiency, sample stability, and regional differences. Results indicate that this model is operationally feasible across multiple countries with a high diagnostic rate, particularly for Gaucher disease and MPS II. The study also revealed challenges such as the impact of tropical climates on sample quality and logistical delays. The article emphasizes the importance of systematic training and standardized testing in improving rare disease diagnosis and care in Africa.

Background Knowledge

Lysosomal Storage Disorders (LSDs) are a group of rare inherited metabolic diseases caused by lysosomal enzyme deficiencies, including Gaucher disease, Pompe disease, Fabry disease, and Mucopolysaccharidosis (MPS). These diseases lead to progressive multisystem damage due to substrate accumulation within cells, with complex and non-specific clinical phenotypes that often result in misdiagnosis or delayed diagnosis. The global incidence is approximately 1 in 7,000–8,000, yet epidemiological data in African populations are extremely limited. Due to shortages of specialists, diagnostic tools, and policy support, rare disease patients in Africa face severe diagnostic challenges. Dried Blood Spot (DBS) technology is a low-cost, easy-to-use method for collecting and transporting biological samples, particularly suitable for remote or resource-limited areas. Already widely used in newborn screening, DBS has recently been extended to genetic disease diagnosis. The 6-plex LSD assay used in this study is based on mass spectrometry and can simultaneously detect six LSD-related enzyme activities, significantly improving screening efficiency. However, challenges remain for widespread application in Africa, including DBS sample stability under high temperature and humidity, logistical bottlenecks in cross-border transportation, and insufficient clinician awareness of rare diseases. Therefore, this study constructed a pilot network across four areas—training, sample transport, testing, and data analysis—to explore a rare disease diagnostic pathway suitable for Africa, fill the research gap in this region, and provide practical foundations for future regional screening programs.

 

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Research Methods and Experiment

The study employed a mixed-methods design, comprising training and diagnostic modules. The training component involved a one-week in-person workshop held from May 30 to June 3, 2022, at the Centre for Human Metabolomics (CHM), North-West University, South Africa, targeting primary care physicians from eight African countries. The curriculum covered fundamentals of rare inherited metabolic diseases, principles of the 6-plex LSD assay, and typical clinical presentations, with case studies used to strengthen diagnostic reasoning. For the diagnostic component, dried blood spot (DBS) sampling kits were distributed to participating countries, enabling physicians to collect samples from suspected LSD patients. Samples were shipped to CHM via local pathology networks or courier services for analysis. The 6-plex LSD assay, based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), quantitatively analyzed six enzyme activities: acid sphingomyelinase (ASM), β-glucocerebrosidase (ABG), acid α-glucosidase (GAA), α-galactosidase (GLA), galactocerebrosidase (GALC), and α-L-iduronidase (IDUA), corresponding to ASMD, Gaucher, Pompe, Fabry, Krabbe, and MPS I diseases, respectively. All samples were registered and analyzed in CHM’s Laboratory Information Management System (Skylims), with abnormal results confirmed via genetic testing. The study also collected data on transportation time, environmental factors, and clinical information to evaluate influencing factors.

Key Conclusions and Insights

• A total of 56 samples were collected over 27 months, identifying 23 LSD patients, yielding a high diagnostic rate of 41%—significantly above the global average—demonstrating that targeted training greatly enhances clinical recognition
• Gaucher disease was the most frequently diagnosed (12 cases), followed by MPS (10 cases, with MPS II accounting for 6), while only one case of Fabry disease was identified, suggesting a need to strengthen screening strategies for this condition
• DBS technology demonstrated excellent stability during international transport, with reliable results obtained even after several months (e.g., average 124 days for samples from Sudan), proving its suitability for remote areas in Africa
• Sample quality was significantly affected by climate, with high humidity in Tanzania and Mozambique leading to false results, indicating the need for improved sample preservation, such as adding desiccants and cooling measures
• Logistical efficiency was closely tied to a country’s access to existing pathology networks; Sudan’s reliance on private couriers caused severe delays, underscoring the necessity of establishing regional diagnostic collaboration networks
• The clinical training received high praise, with participants recommending a hybrid online/offline format in the future to broaden reach and suggesting case-sharing sessions to enhance interactivity

Research Significance and Outlook

This study represents the first systematic evaluation of DBS technology for rare disease diagnosis across multiple sub-Saharan African countries, confirming its feasibility and efficiency in resource-limited settings. It not only established cross-border sample transportation and analysis workflows but also identified training, climate, and logistics as three key influencing factors, providing a replicable model for future regional screening programs. The high diagnostic rate indicates a large number of undiagnosed LSD patients in Africa, highlighting the urgent need to expand screening. Future research should increase sample sizes, include more countries, and optimize sample preservation strategies to address tropical climate challenges. Additionally, establishing local diagnostic centers in Africa could reduce dependence on South Africa and improve response times. Furthermore, integrating genomic sequencing (e.g., WES/WGS) to analyze cases with normal enzyme activity but strong clinical suspicion may uncover novel pathogenic genes or variants. Through sustained physician education, policy advocacy, and international collaboration, it may be possible to gradually close the gap in rare disease diagnosis and care between Africa and other regions.

 

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Conclusion

This study demonstrates the initial success of establishing a rare disease diagnostic network in sub-Saharan Africa. By combining systematic clinical training with dried blood spot testing, the research team achieved effective sample collection and analysis across eight countries, achieving high diagnostic rates, particularly for Gaucher disease and MPS II. This indicates that, despite challenges such as logistical delays, climate impacts, and shortages of specialized personnel, Africa has the potential to conduct rare disease screening. Dried blood spot technology has proven to be stable and suitable for remote transport, delivering reliable data even under extreme conditions. However, tropical high-humidity environments threaten sample quality, requiring improved preservation methods such as desiccants and temperature control. The study emphasizes the importance of establishing regional collaborative networks and standardized operating procedures. Future efforts should expand physician coverage through hybrid training models, promote localized diagnostic capacity, and integrate genomic approaches to improve diagnostic rates. Ultimately, such projects will not only help identify patients and enable early intervention but also contribute to the accumulation of epidemiological data on rare diseases in African populations, informing policy-making and healthcare resource allocation, thereby systematically enhancing rare disease diagnosis and care in the region.

 

Albe Carina Swanepoel, Christian Johannes Hendriksz, Renson Mukhwana, Roselyn Odero, and Engela Helena Conradie. Improving access to rare disease diagnostics in Africa: insights from a multinational pilot study. Orphanet Journal of Rare Diseases.