Orphanet Journal of Rare Diseases | Retrospective Analysis of the Diagnostic Journey of Fabry Disease Patients

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This study is based on two large U.S. insurance claims databases and analyzes symptoms, comorbidities, and healthcare resource utilization in Fabry disease patients within two years prior to diagnosis. The results show that patients experienced a wide range of cardiovascular, neurological, and gastrointestinal symptoms before diagnosis, along with significant diagnostic delays, offering important clues for improving early recognition of Fabry disease.

 

Literature Summary
The article titled 'Patient journey to Fabry disease diagnosis in the United States: an observational retrospective analysis of two United States claims databases' was published in Orphanet Journal of Rare Diseases. It reviews and summarizes the medical journey of Fabry disease patients before diagnosis. The study used two U.S. claims databases, Optum Clinformatics® Data Mart (Optum CDM) and Komodo Research Dataset (Komodo RD), to analyze clinical manifestations, comorbidities, medication use, and healthcare utilization within two years prior to diagnosis. The article notes that Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to reduced or absent α-galactosidase A (α-Gal A) activity, which results in the accumulation of glycosphingolipids (e.g., GL-3) in multiple organs and causes clinical manifestations such as neuropathic pain, gastrointestinal dysfunction, renal failure, hypertrophic cardiomyopathy, arrhythmia, heart failure, and stroke. Patients commonly experience multisystem symptoms before diagnosis, with significant differences between males and females. The study also highlights the importance of gender differences in disease manifestations. Early recognition and intervention are crucial for improving patient outcomes.

 

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Research Methods and Experiments
This study is a retrospective, observational analysis based on two large U.S. insurance claims databases (Optum Clinformatics® Data Mart and Komodo Research Dataset) to explore the diagnostic journey of Fabry disease patients. A total of 201 patients (Optum CDM) and 923 patients (Komodo RD) diagnosed between March 31, 2012, and March 31, 2022 (Optum CDM), and between January 1, 2018, and September 30, 2022 (Komodo RD), were included. The study analyzed clinical symptoms, comorbidities, medication use, and healthcare utilization within two years prior to diagnosis. By using ICD-9 and ICD-10 diagnostic codes, drug reimbursement records, specialist visit frequencies, hospitalization and emergency department visits, the study assessed the disease burden and healthcare-seeking behaviors before diagnosis.

Key Findings and Perspectives

• Within two years prior to diagnosis, Fabry disease patients commonly experienced cardiovascular (72.6% Optum CDM, 56.4% Komodo RD), neurological (64.2% and 59.3%), gastrointestinal (46.3% and 51.2%), and mental health-related symptoms (32.8% and 36.5%).
• Female patients showed higher incidence of gastrointestinal and mental health symptoms compared to male patients, while males had more frequent cardiovascular- and renal-related hospitalizations.
• In the two years before diagnosis, patients averaged up to 45 visits (Optum CDM) and 23 visits (Komodo RD).
• More than 40% of patients had visited the emergency department, indicating frequent healthcare encounters before diagnosis.
• Healthcare resource utilization increased significantly in the year before diagnosis, especially in female patients, with a notable rise in emergency visits and laboratory tests.

Significance and Future Directions
The study reveals a significant multisystem disease burden in Fabry patients prior to diagnosis, highlighting the need for clinicians to be vigilant about nonspecific symptoms to reduce diagnostic delays. Future efforts should focus on interdisciplinary collaboration, implementing early screening strategies, and integrating genetic testing and biomarker analysis to enhance diagnostic efficiency. Additionally, targeted genetic testing in patients with high-risk conditions such as chronic kidney disease or hypertrophic cardiomyopathy should be considered to facilitate early intervention and treatment.

 

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Conclusion
Prior to diagnosis, Fabry disease patients commonly exhibit multisystem symptoms, including cardiovascular, neurological, gastrointestinal, and mental health issues, with significant differences in symptom presentation between males and females. The study emphasizes the importance of early recognition and screening to prevent long-term organ damage and improve patient outcomes. Through interdisciplinary collaboration, red-flag alerts in electronic health records, and integration of genetic testing, early diagnosis rates may be improved, providing better treatment opportunities for patients. This study offers valuable insights into the diagnostic pathways for rare diseases and provides empirical evidence for future real-world data-driven diagnostic optimization strategies.

 

Alexandra Dumitriu, Gandarvaka Miles, Ana Crespo, Roberto Araujo, and Natalia Petruski-Ivleva. Patient journey to Fabry disease diagnosis in the United States: an observational retrospective analysis of two United States claims databases. Orphanet Journal of Rare Diseases.