Edition of 03 August 2023

A new article has been published in Nature Biotechnology, which illustrates the challenges of diagnosing and treating “nano-rare” disease by presenting the case study of a 13-year old boy with such a condition.

The term “nano-rare” is used to refer to monogenic conditions whose prevalence is only 1-30 individuals worldwide. Their populations, in addition to being exceptionally small, are typically geographically scattered. They therefore face unique challenges in diagnosis, identification, and treatment.

The case presented in this article is that of a 13-year old boy who has experienced a range of severe symptoms beginning at a young age, and which were eventually linked to a mutation in the SCN2A gene. To date, only 9 patients with such a mutation have been reported worldwide, all of whom exhibit similar symptoms. Because of the rarity of the condition, the patient’s family faced nearly insurmountable obstacles in obtaining a diagnosis. Once a diagnosis was made, they also faced challenges in locating clinicians willing to take on the child’s care.

These experiences point to the existing weaknesses in how integrated, genomically-directed care is provided for patients with nano-rare conditions. However, there is also an opportunity to learn from them and rethink the ways genetics-based care delivery is approached in health systems more broadly. While improving the quality of care available to nano-rare individuals, it would also facilitate an advancement in our understanding of molecular pathogenesis, and could prove cost-saving. In particular, the authors reference the work of the Undiagnosed Diseases Network as providing a model for how improved health outcomes can be delivered at a lower cost.

A new article published in the Orphanet Journal of Rare Diseases presents the E-Merge project and its efforts to synchronise data between three large European registries for autoinflammatory diseases (AID), performed in line with the Metadata registry for the ERN RITA (MeRITA) and supported by the Paediatric Rheumatology European Association’s EMERGE fellowship program.

Currently, there are three main registries which collect information on AID in Europe: Eurofever, JIRcohort, and AID-net. Synchronising the data contained in the three would provide a more robust body of evidence on these rare conditions, and would help facilitate future epidemiological and clinical research.

To this end, the E-Merge project worked to test the possibility of collectively analysing data collected from different registries. Researchers found that there was sufficient homogeneity in the variables recorded in each registry such as to make such synchronisation feasible. They also determined that the majority of patients enrolled in the three registries were from Western and Southern Europe, indicating a high level of potential for further cooperation in Eastern Europe to address underdiagnosis of AID.

The authors identify a number of challenges which have been encountered in similar data synchronisation projects. These include:

• The possibility of multiple entries of the same patient into different registries;
• Difficulties with detailed data analysis due to differences in granularity across registries;
• The need for a standardised follow-up protocol so that longitudinal data can be accurately compared between studies and cohorts;
• Limitations on how complex statistical analyses can be which arise from data aggregation.

Overall, this study highlights the need for collaboration in studying AID and other rare conditions, and demonstrates the potential of data synchronisation to help facilitate such efforts. By standardising clinical data and longitudinal follow-up monitoring, data collection can be optimised for future research and cooperation efforts.