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

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This article provides French national diagnostic and treatment guidelines for Gaucher disease, covering clinical management, genetic counseling, biomarkers, and therapeutic 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 the latest national guidelines for Gaucher disease (GD). GD is an autosomal recessive lysosomal disorder caused by β-glucocerebrosidase (GBA1) deficiency, with an incidence rate of approximately 1/130,000 in France. The study outlines three major clinical subtypes: GD1 (95%), GD2 (<1%), and GD3 (<5%), emphasizing the importance of early diagnosis and personalized treatment. It discusses diagnostic criteria, biomarker testing, imaging assessment, and the role of multidisciplinary teams in optimizing patient care.

Background Knowledge
Gaucher disease (GD) is a rare lysosomal storage disorder caused by GBA1 gene mutations leading to β-glucocerebrosidase dysfunction and subsequent accumulation of glucosylceramide in macrophages. GD1 (non-neuronopathic) presents with hepatosplenomegaly, cytopenia, and bone complications. GD2 (acute neuronopathic) and GD3 (chronic neuronopathic) involve progressive neurological symptoms manifesting in infancy and adolescence/adulthood respectively. Current treatments include enzyme replacement therapy (ERT) and substrate reduction therapy (SRT), though standardized treatment cessation criteria remain undefined. This update, based on the French Gaucher disease registry (RFMG) and PNDS protocol, offers systematic guidance on diagnosis, therapy, and follow-up. Additional topics include genetic counseling, imaging assessment, bone density monitoring, and multidisciplinary collaboration requirements.

 

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Research Methods and Experimental Design
The study systematically reviewed GD clinical manifestations, diagnostic criteria, therapeutic strategies, and follow-up protocols through the French Gaucher disease registry (RFMG) and national management guidelines (PNDS). The research team comprised the Gaucher Expert Committee (CETG) and Lysosomal Diseases Reference Centers (CRML), applying methodology recommended by the French National Authority for Health (HAS) to ensure scientific and clinical validity. Diagnostic emphasis was placed on β-glucocerebrosidase enzyme activity testing and GBA1 gene sequencing, with plasma biomarkers (LysoGL1, chitotriosidase, CCL18) recommended for auxiliary diagnosis. Imaging protocols included MRI, bone densitometry, and X-rays for assessing skeletal and visceral involvement. The study systematically analyzed ERT and SRT indications, dose adjustments, drug switching, and long-term management, highlighting the necessity of multidisciplinary teams in therapeutic decision-making.

Key Findings and Perspectives

• GD incidence in France is approximately 1/130,000, with GD1 accounting for 95% of cases, GD2 <1%, and GD3 <5%.
• GD diagnosis primarily relies on β-glucocerebrosidase enzyme activity testing confirmed by GBA1 gene sequencing, with plasma biomarkers (LysoGL1, chitotriosidase, CCL18) serving as auxiliary tools.
• Therapeutic strategies require individualization based on clinical, biological, and imaging criteria. ERT (e.g., imiglucerase, velaglucerase alpha) and SRT (e.g., eliglustat, miglustat) are primary treatment modalities, with eliglustat approved by EMA in 2025 for GD1 pediatric patients aged ≥6 years and weight ≥15kg.
• Treatment goals include alleviating anemia, thrombocytopenia, hepatosplenomegaly, bone complications, and improving quality of life. Treatment response can be monitored through biomarker level reductions and imaging improvements.
• Bone-related complications (bone pain, osteonecrosis, osteoporosis) require multidisciplinary management including rehabilitation, orthopedic interventions, and pain management.
• Follow-up should include annual clinical evaluations, biomarker monitoring, and imaging assessments, extendable to 3-4 years for stable patients.
• Genetic counseling and prenatal diagnosis are emphasized, particularly for high-risk families through GD2/GD3 carrier screening.

Research Significance and Future Directions
This study provides authoritative guidance for standardizing GD diagnosis and management, enabling personalized treatment plans while highlighting the importance of early intervention and long-term follow-up. Future developments may integrate gene therapy, targeted interventions, and AI-assisted diagnostic tools to improve treatment adherence and patient quality of life. The guidelines also serve as a template for national protocols addressing other rare diseases.

 

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Conclusion
This article systematically summarizes the French national guidelines (PNDS) for Gaucher disease management, covering clinical subtypes, diagnostic protocols, therapeutic strategies, and follow-up procedures. GD1 (non-neuronopathic) exhibits variable clinical manifestations ranging from asymptomatic to severe bone complications and organomegaly. GD2 and GD3 present with acute fatal neurological manifestations in infancy and progressive neurological symptoms in adolescence/adulthood respectively. The study emphasizes the critical role of multidisciplinary teams in GD management, with ERT and SRT as primary therapeutic approaches. Genetic testing and biomarker analysis (LysoGL1, chitotriosidase) provide essential diagnostic and monitoring tools. Imaging modalities (MRI, bone densitometry) enable effective assessment of skeletal and visceral involvement. These guidelines establish a standardized management framework for Gaucher disease patients and serve as a reference template for global rare disease protocols. Additionally, the study identifies future research priorities including treatment cessation 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.