Orphanet Journal of Rare Diseases | KLINSE Clinical Information Center Supports Rare Disease Diagnosis and Management

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This study introduces KLINSE, a rare disease clinical information center established at the University of Tübingen in Germany, which provides timely and professional support for clinicians through a systematic service model, significantly improving the efficiency of managing complex cases.

 

Literature Overview

The article titled 'KLINSE: a comprehensive service model for rare disease information and care management support,' published in the journal *Orphanet Journal of Rare Diseases*, reviews and summarizes the operational model, service workflow, and analysis of the first 100 cases of KLINSE, a clinical information center established in 2021 at the University of Tübingen’s rare disease center. The study shows that KLINSE, as a physician-to-physician service platform, effectively fills the gap in post-diagnostic treatment and management information for rare diseases, with particularly high demand among pediatric and adolescent patients. By systematically searching international databases, contacting domain experts, and integrating treatment options and patient organization information, the service provides strong support for clinical decision-making. The study also reveals systemic challenges in current rare disease care, such as delayed information access and fragmented resources, validating the value of the KLINSE model in enhancing continuity of care.

Background Knowledge

Rare diseases are defined as disorders affecting fewer than 1 in 2,000 individuals in Europe. Over 8,000 rare diseases are currently known globally, with approximately 85% classified as ultra-rare (<1/1,000,000). Although individual diseases have few patients, the total affected population is large—around 4 million in Germany alone. About 70% of rare diseases have a genetic basis, and high-throughput sequencing has significantly improved diagnostic rates. However, treatment and management after diagnosis remain major challenges. Most rare diseases lack clinical guidelines, exhibit strong phenotypic heterogeneity, and have complex genotype-phenotype correlations, with rapidly evolving knowledge that makes it difficult for non-specialists to access timely and accurate information. Additionally, patients often endure a 'diagnostic odyssey' and then face a 'treatment and management odyssey' after diagnosis. While existing databases such as Orphanet, OMIM, and GeneReviews offer foundational information, they lack personalized and dynamically updated clinical recommendations. Thus, there is an urgent need for a low-threshold, expert-driven, and rapidly responsive clinical support system. KLINSE was established precisely in this context, aiming to bridge the gap between diagnosis and treatment and improve the overall quality of rare disease care. Its service model integrates systematic literature reviews, expert consultations, patient organization outreach, and personalized report generation, forming a closed-loop support system. This study provides empirical evidence for building scalable rare disease clinical support networks in the future.

 

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Research Methods and Experiments

The research team launched the KLINSE service in May 2021, increasing awareness through targeted promotion to pediatric centers, genetics departments, and adult disability care centers. Submitted cases must meet two core criteria: a confirmed rare disease diagnosis with clear genetic evidence. Submission materials include genetic reports and data privacy consent forms. Eligible cases are categorized as 'comprehensive consultation' or 'brief consultation' and undergo systematic searches based on a predefined protocol, covering resources such as Orphanet, OMIM, PubMed, GeneReviews, and clinical trial registries. The research covers disease mechanisms, clinical manifestations, treatment options, monitoring recommendations, natural history, guidelines, expert centers, clinical trials, and patient organizations. After evaluation by the KLINSE clinical team, standardized information letters are generated and sent via email or post, accompanied by a feedback form to assess service quality. Cases not meeting the criteria are rejected and advised to undergo further testing or referral.

Key Findings and Insights

• Between May 2021 and November 2023, KLINSE received 100 submissions, of which 88 were accepted—66 comprehensive and 22 brief consultations
• 58% of consultations were initiated within one year of genetic diagnosis, though some were delayed up to 10 years, reflecting information access lag
• 71% of cases involved ultra-rare diseases (<1/1,000,000), and 46 had fewer than 100 reported cases in the literature, highlighting information scarcity
• The most frequently requested topics were treatment options (37/88), clinical trials and registries (36/88), expert centers (35/88), and patient organizations (32/88)
• 74% of submitters requested more than two specific services, indicating complex and multidimensional clinical needs
• While core information (e.g., clinical features) was generally available, natural history data was accessible in only 58% of cases, treatment information in 78%, and targeted therapies existed in only four cases
• KLINSE proactively provided clinically valuable but unrequested information—such as expert centers and patient organizations—in 57% of cases
• Among 40 feedback responses, 95% of submitters reported all questions fully answered, 97.5% found the information scope met or exceeded expectations, and 77.5% considered the information directly clinically relevant to patient management
• Follow-up feedback from the largest submitting institution (Social Pediatric Center) indicated that KLINSE’s findings exceeded the capabilities of non-university medical facilities and significantly influenced the management of three specific cases, including initiating brain MRI, clarifying diagnosis, and establishing co-management with expert centers

Research Significance and Outlook

The successful implementation of KLINSE validates the feasibility and high value of an expert-driven, low-threshold clinical support model in rare disease management. This model effectively reduces the information retrieval burden on non-specialists, improves diagnostic and treatment efficiency and quality, and is particularly suitable for resource-limited primary care settings. Its structured process ensures systematic and traceable information delivery, while proactive provision of supplementary information enhances the forward-looking nature of the service.

Future directions include expanding geographical coverage, strengthening collaboration with international rare disease networks (e.g., Treatabolome), and exploring AI-assisted information mining to improve efficiency. The research team also plans to advocate for integrating this model into routine healthcare services and securing insurance reimbursement to ensure sustainability and scalability. This service provides a replicable model for global rare disease care systems, emphasizing the importance of cross-institutional collaboration and knowledge sharing.

 

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Conclusion

This study systematically evaluates the effectiveness of the KLINSE clinical information center in supporting rare disease diagnosis and management. Analysis of the first 100 submitted cases reveals widespread delays and resource shortages in post-diagnosis information access, particularly in the field of ultra-rare diseases. KLINSE effectively addresses this gap by delivering timely, structured, and multidimensional clinical knowledge. Its services not only respond to specific inquiries but also proactively provide additional clinically valuable information, significantly enhancing physicians’ decision-making capabilities. Feedback data confirms the service’s high practicality and clinical relevance. The successful operation of KLINSE demonstrates that establishing specialized, expert-driven clinical support platforms is a key strategy for improving the quality of care for rare disease patients. The model shows strong scalability, and if integrated with AI technologies and supported by healthcare systems in the future, it has the potential to become a standard component of global rare disease management, fundamentally shortening patients’ 'treatment and management odyssey' and improving overall health outcomes. This study provides important empirical evidence and a practical roadmap for building efficient and sustainable rare disease support networks.

 

Katrin Jäger, Elke Dannenmann-Stern, Sevda Inbasi, Christina Vossler-Wolf, and Holm Graessner. KLINSE: a comprehensive service model for rare disease information and care management support. Orphanet Journal of Rare Diseases.