Orphanet Journal of Rare Diseases | Update on French Gaucher Disease Diagnosis and Treatment Guidelines

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This article provides the national diagnostic and therapeutic guidelines for Gaucher disease in France, covering clinical management, genetic counseling, biomarkers, and treatment strategies. It establishes a standardized framework for multidisciplinary management of Gaucher disease patients.

 

Literature Overview
This article, titled 'French national diagnosis and care protocol (Protocole National De Diagnostic et de Soins; PNDS): Gaucher disease', published in Orphanet Journal of Rare Diseases, reviews and summarizes the latest national diagnostic and therapeutic guidelines for Gaucher disease (GD). GD is an autosomal recessive lysosomal disorder caused by deficiency of β-glucocerebrosidase (GBA1), with an incidence of approximately 1/130,000 in France. The study outlines three major clinical subtypes of GD: GD1 (95%), GD2 (<1%), and GD3 (<5%), emphasizing the importance of early diagnosis and individualized treatment. It also discusses diagnostic criteria, biomarker testing, imaging evaluation, and the role of multidisciplinary treatment teams, aiming to provide optimal management strategies for healthcare professionals.

Background Knowledge
Gaucher disease (GD) is a rare lysosomal storage disorder caused by GBA1 gene mutations leading to functional deficiency of β-glucocerebrosidase, resulting in glucosylceramide accumulation in macrophages. GD1 is the most common form, characterized by splenomegaly, hepatomegaly, cytopenia, and bone abnormalities. GD2 and GD3 are associated with early-onset lethal neurological manifestations and juvenile/adult-onset progressive neurological symptoms, respectively. Current treatments for GD include enzyme replacement therapy (ERT) and substrate reduction therapy (SRT), but lack defined treatment discontinuation criteria. This study, based on the French Gaucher Disease Registry (RFMG) and national management protocol (PNDS), systematically updates GD diagnosis, treatment, and follow-up approaches to help medical teams better manage patients. Additionally, it discusses genetic counseling, imaging evaluation, bone mineral density monitoring, and the necessity of multidisciplinary collaboration, providing a comprehensive clinical management framework for Gaucher disease.

 

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Research Methods and Experiments
This study systematically reviews GD clinical manifestations, diagnostic criteria, treatment strategies, and follow-up requirements based on the French Gaucher Disease Registry (RFMG) and national management protocol (PNDS). The research team, composed of the Committee of Experts on Gaucher Disease (CETG) and the National Reference Center for Lysosomal Diseases (CRML), employed methodology recommended by the French Health Authority (HAS) to ensure scientific validity and clinical applicability. For diagnosis, the study emphasizes β-glucocerebrosidase activity testing and GBA1 gene mutation analysis, recommending plasma biomarkers LysoGL1, chitotriosidase, and CCL18. Imaging evaluations include MRI, bone densitometry, and X-rays for assessing skeletal and visceral involvement. Regarding treatment, the study systematically analyzes indications, dose adjustments, drug switching, and long-term management for ERT and SRT, highlighting the role of multidisciplinary teams in treatment decisions.

Key Conclusions and Perspectives

• Gaucher disease (GD) has an incidence of approximately 1/130,000 in France, with GD1 as the most common clinical subtype (95%), followed by GD2 (<1%) and GD3 (<5%).
• GD diagnosis primarily relies on β-glucocerebrosidase activity measurement confirmed by GBA1 gene sequencing, with plasma biomarkers (LysoGL1, chitotriosidase, CCL18) recommended as auxiliary diagnostic tools.
• Treatment strategies should be individualized based on clinical, biological, and imaging criteria. ERT (e.g., imiglucerase and velaglucerase alpha) and SRT (e.g., eliglustat and miglustat) are the main therapeutic approaches, with eliglustat approved by EMA in 2025 for GD1 pediatric patients over 6 years old weighing ≥15kg.
• Treatment objectives include alleviating anemia, thrombocytopenia, hepatosplenomegaly, bone abnormalities, and improving quality of life. Treatment response can be evaluated through decreased biomarker levels and improved imaging findings.
• For bone-related complications including bone pain, avascular necrosis, and osteoporosis, multidisciplinary management is recommended, incorporating rehabilitation, orthopedic interventions, and pain management.
• Follow-up should include annual clinical evaluations, biomarker monitoring, and imaging assessments, with stable patients extending intervals to every 3-4 years.
• The study emphasizes the importance of genetic counseling and prenatal diagnosis, particularly in high-risk families, including carrier screening for GD2 and GD3.

Research Significance and Future Perspectives
This study provides authoritative guidance for standardizing GD diagnosis and treatment, helping clinicians develop individualized therapeutic plans while emphasizing early intervention and long-term follow-up. Future GD management may integrate gene therapy, targeted interventions, and AI-assisted diagnostic tools to improve treatment adherence and quality of life. Additionally, these guidelines serve as a reference template for developing national diagnostic protocols for other rare diseases.

 

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Conclusion
This article systematically summarizes the French national diagnostic and treatment guidelines (PNDS) for Gaucher disease, covering clinical subtypes, diagnostic procedures, treatment strategies, and follow-up management. GD1 is the most common subtype with diverse clinical manifestations ranging from asymptomatic to severe bone abnormalities and organ enlargement. GD2 and GD3 demonstrate early lethal and progressive neurological features respectively. The study emphasizes the critical role of multidisciplinary teams in GD management and recommends ERT and SRT as primary treatment modalities. Genetic testing and biomarker analysis (e.g., LysoGL1, chitotriosidase) have significant value in diagnosis and follow-up. Imaging examinations (e.g., MRI, bone density) help assess skeletal and visceral involvement. This guideline provides a standardized management framework for Gaucher disease patients and serves as a reference for global rare disease protocols. Additionally, the article identifies future research needs including treatment discontinuation criteria, gene therapy potential, and complication prevention strategies.

 

Fabrice Camou, Christine Serratrice, Magali Pettazzoni, Marc G Berger, and Nadia Belmatoug. French national diagnosis and care protocol (Protocole National De Diagnostic et de Soins; PNDS): Gaucher disease. Orphanet Journal of Rare Diseases.