Tackling the Silent Struggle: Understanding and Addressing Pain in Children with Mucopolysaccharidoses
Imagine a young child battling a rare genetic condition, where persistent pain lurks beneath the surface of their daily life, often slipping through the cracks of medical evaluation and care. This isn't just a hypothetical scenario—it's the harsh reality for many kids with mucopolysaccharidoses (MPS), a group of inherited lysosomal storage disorders that can severely impact their health and well-being. But here's where it gets intriguing: while pain is a hallmark of these conditions, accurately identifying and managing it remains a formidable challenge. Dive into this comprehensive exploration of a groundbreaking French study, and you'll uncover why pain assessment in pediatric MPS patients is more complex than it seems—and why bridging the gap between patient experiences and clinical perceptions could transform lives.
Research Overview
This piece delves into an open-access research article published on November 12, 2025, in the Orphanet Journal of Rare Diseases (volume 20, article number 581). For those new to academic publishing, open access means the full study is freely available online through platforms like Springer Nature, allowing anyone to read and build upon the findings without paywalls.
Key Contributors
The work was led by a team of experts: Mélanie Blin, Marine Tardieu, Didier Lacombe, Magali Gorce, Léna Damaj, Magalie Barth, Delphine Genevaz, Sophie Vibet, and François Labarthe (corresponding author, with an ORCID ID for verification: orcid.org/0000-0001-9788-9667). Affiliated with esteemed institutions like the Centre de Référence Maladies Héréditaires du Métabolisme ToTeM in Tours, France, and others across Bordeaux, Toulouse, Rennes, and Angers, these researchers bring a wealth of clinical and scientific insight.
Abstract: Unveiling the Pain Paradox in Pediatric MPS Care
Mucopolysaccharidoses, or MPS for short, encompass a family of genetic lysosomal storage diseases that vary widely in severity. These conditions can lead to symptoms like cognitive impairments, skeletal deformities, short stature, vision problems, cardiovascular issues, and respiratory challenges. Chronic pain, lasting three months or longer, is a common complaint among affected children, manifesting as joint stiffness (nociceptive pain), nerve-related issues like carpal tunnel syndrome (neuropathic pain), or heightened sensitivity to touch. For beginners wondering what nociceptive pain means, think of it as pain from tissue damage, like a sprained ankle, while neuropathic pain stems from nervous system dysfunction, often described as tingling or burning.
The goal of this multicenter French study was to investigate how pain is identified and handled in young MPS patients. Researchers reviewed medical records from five specialized metabolic disorder centers and conducted a nationwide online survey capturing insights from patients, families, and healthcare providers.
Drawing from data on 48 pediatric MPS cases, the findings painted a stark picture: pain was widespread and recurring, appearing in 94% of patients. Yet, evaluating it proved notoriously tricky. Medical documentation showed consistent pain assessments and interventions, with families reporting frequent, intense pain. Surprisingly, healthcare professionals felt content with their approaches, believing most patients were pain-free. This mismatch raises eyebrows—could it stem from communication breakdowns or inadequate tools?
To improve matters, the study advocates for routine, tailored pain evaluations, especially in outpatient settings, using suitable scales for kids with disabilities. Training for caregivers and partnerships with pain management specialists are also emphasized. Ultimately, a standardized pain protocol adaptable to all MPS patients, including those with cognitive or motor challenges, is urgently needed.
Highlights: Key Takeaways at a Glance
- Persistent pain plagues many children with MPS, but spotting and treating it demands specialized attention.
- Customized tools for pain detection are essential, particularly for those with cognitive impairments, and should adopt a holistic approach that considers sensory, emotional, social, cognitive, and behavioral factors.
- Empowering caregivers through education and fostering collaborations with pain clinics are critical steps forward.
Introduction: The Hidden Burden of MPS and Its Painful Reality
Mucopolysaccharidoses represent a cluster of rare genetic lysosomal storage diseases, with seven subtypes showing varying degrees of severity. Lysosomes are like tiny recycling centers in cells, and when they malfunction, harmful substances build up, causing widespread damage. Symptoms often include cognitive delays, skeletal and joint issues, shortened height, facial coarsening, vision loss, heart and lung problems. Chronic pain is a prevalent issue in MPS kids, involving different types: nociceptive (e.g., from enlarged organs like the liver or spleen), neuropathic (such as spinal injuries or carpal tunnel), and sensory over-sensitivity.
Detecting and alleviating this pain is particularly arduous in children with cognitive challenges, as noted in prior studies. Effective pain management can significantly enhance quality of life, as seen in a subset of MPS type IV-A patients who benefited from better care. Yet, research on pain in MPS is limited, prompting this investigation into assessment and treatment practices across French centers.
Patients and Methods: A Dual-Approach Investigation
The study combined retrospective medical record reviews with a national online survey, ensuring a rounded perspective on pain experiences.
Retrospective Analysis of Medical Records
Data came from five metabolic disorder centers in Angers, Bordeaux, Rennes, Toulouse, and Tours. Inclusion criteria focused on confirmed MPS cases in children under 19, with at least two follow-up visits. Ethical approval from the University Hospital of Tours' committee ensured patient privacy, with informed consent from all participants.
Pain-related details were extracted from records over the past five years, focusing on the three most recent visits per type (outpatient consultations, day-hospital stays, and inpatient admissions). Beyond demographics, researchers noted pain scale usage, descriptive terms like "painful" or "analgesic," treatment prescriptions, and post-treatment follow-ups.
Online Survey for Insights from Families and Professionals
Using Survio.com, anonymous surveys were distributed via the French network for inherited metabolic diseases (Filière G2M) and the patient association Vaincre les Maladies Lysosomales. A follow-up reminder was sent after 15 days.
The family survey (detailed in the journal's supplementary materials) included 26 questions on patient history, pain expressions, frequency, intensity, and treatment experiences. The professional survey (also supplementary) had 19 questions on pain management practices and perceptions, completed by physicians and nurses with MPS experience.
Statistical Analysis
Results were summarized with medians, ranges, or percentages. Comparisons used tests like Kruskal-Wallis, Dunn's, chi-square, and Spearman, with significance set at p < 0.05. Analysis was done via GraphPad Prism 6.0.
Results: Unearthing Discrepancies in Pain Perception
The retrospective review covered 48 MPS patients, with MPS-I as the most common, followed by MPS-II and MPS-III. Males predominated, likely due to the X-linked nature of MPS-II. Many received enzyme replacement therapy (ERT) or hematopoietic stem cell transplants. Clinical features ranged from skeletal abnormalities to cognitive and respiratory issues, with 38% having carpal tunnel syndrome. Supportive aids like wheelchairs and medications were common.
Pain Evaluation and Management Insights from Records
Across 252 visits (89 outpatient, 98 day-hospital, 65 inpatient), pain was documented in 72% of cases, though scales were specified in only half. Popular tools included the Face Pain Scale-Revised (FPS-R, 34%), FLACC (24%), EVENDOL (15%), Numerical Rating Scale (13%), and Verbal Scale (8%), with rarer ones like HEDEN or CHEOPS.
Pain was reported in 60 instances (33% of assessments), affecting 94% of patients. Treatments followed in two-thirds of cases, often analgesics (paracetamol or NSAIDs), referrals to specialists, or physiotherapy. Reassessment occurred in 66% of treated cases, deemed effective 41% of the time.
Day-hospital and inpatient visits saw more assessments, but outpatient ones lagged. Pain was more frequent in outpatient settings. For MPS subtypes, assessments were lower in MPS-III (59%) versus others (72-88%). Factors influencing assessments included disabilities requiring equipment, ERT, or symptoms like carpal tunnel, but not psychomotor delays. Pain correlated with chronic analgesic use, prior pain consultations, skeletal issues, carpal tunnel, age, and follow-up duration, but inversely with psychomotor delays.
National Survey: Voices from Families and Professionals
Fifty-three families responded, representing various MPS types. Pain manifested through verbal complaints or grimacing, with high intensity noted. Assessments typically involved family discussions, rarely scales. Treatments included analgesics or non-drug options, with some self-medication and opioid use. One patient tried cannabidiol.
Twenty-one professionals (12 physicians, 9 nurses) felt equipped with tools, protocols, and training. Most (81%) reported regular assessments, but estimated pain in under 50% of patients. They expressed satisfaction with their pain-related practices.
Discussion: Bridging the Gap and Sparking Debate
This study confirms chronic pain as a frequent MPS companion, aligning with global literature. But here's where it gets controversial: the stark contrast between detailed medical records of assessments, families' reports of relentless pain, and professionals' contentment with low-pain perceptions. Is this a failure of communication, or do outdated tools mask true suffering? And this is the part most people miss: underestimating pain might stem from focusing only on physical sensations, ignoring emotional, social, and psychological layers—a multidimensional oversight that could leave patients underserved.
Pain evaluations were robust in hospital settings due to quality metrics, but outpatient care fell short, possibly prioritizing urgent issues. For MPS-III patients, assessments were rarer, perhaps due to fewer hospital therapies and cognitive barriers. Specific scales for disabilities are vital, as generic ones fail. Questioning scales' appropriateness could fuel debate: are we using tools that truly capture pediatric MPS pain, or sticking to tradition?
The survey highlighted families' unawareness of disability-tailored tools, underscoring training needs. Expanding, imagine a child with MPS-III who can't verbally express pain—without trained caregivers using behavioral cues like facial expressions or agitation, their discomfort might go unnoticed. This calls for education campaigns.
Drug treatments leaned on basics like paracetamol and NSAIDs, with opioids rare and cannabidiol experimental. Nondrug options like massage or chiropractic care were underutilized despite proven benefits in reducing pain and anxiety in kids. Cost barriers and limited access to pain centers were noted. Controversially, while ERT shows promise in preventing pain, emerging therapies like anti-TNF-α (inflammation fighters) remain untapped in humans—could this be a missed opportunity, or too risky for children?
Improving family-professional dialogue, raising awareness of high pain prevalence, and multidimensional approaches (sensory-discriminative, affective, cognitive, behavioral, sociocultural) are recommended. Tools like the Pediatric Pain Profile (PPP) for acute/chronic pain in disabled kids could revolutionize assessment.
Limitations include the retrospective design (possible undocumented inquiries) and small sample, but it reflects French MPS demographics. Future work should incorporate quality-of-life measures, as chronic pain can erode well-being despite treatments like ERT.
Conclusion: A Call for Action and Reflection
Chronic pain plagues MPS children yet evades adequate detection and relief, exposing gaps between patient needs and professional practices. Standardized pain protocols, tailored scales, caregiver training, and pain center partnerships are essential. Pain education in medical curricula could prevent underestimation, ensuring holistic care.
As pain intertwines with quality of life, developing adaptable protocols for all MPS subtypes—even those with neurocognitive impairments—is paramount. This study paves the way for prospective, national efforts.
What do you think? Is the discrepancy between patient reports and professional perceptions inevitable in rare diseases, or a symptom of broader healthcare flaws? Do you agree that multidimensional pain models are the future, or should we focus more on accessible therapies? Share your thoughts in the comments—let's debate and drive change for these vulnerable children.
Data Availability
Datasets are obtainable from the corresponding author upon request.
Acknowledgments
Gratitude to Vaincre les Maladies Lysosomales for survey distribution.
Funding
No external funding was received.
Author Information
- Mélanie Blin, Marine Tardieu, François Labarthe: Centre de Référence Maladies Héréditaires du Métabolisme ToTeM, CHRU Tours, Tours, France; N2C, Inserm U1069, Université François Rabelais de Tours, Tours, France (Labarthe).
- Didier Lacombe: Inserm U1211, Université de Bordeaux, Centre de Compétences Maladies Héréditaires du Métabolisme, CHU de Bordeaux, Bordeaux, France.
- Magali Gorce: Centre de Référence Maladies Héréditaires du Métabolisme, CHU Toulouse, Toulouse, France.
- Léna Damaj: Centre de Compétences Maladies Héréditaires du Métabolisme, CHU Rennes, Rennes, France.
- Magalie Barth: Centre de Compétences Maladies Héréditaires du Métabolisme, CHU Angers, Angers, France.
- Delphine Genevaz: Vaincre les Maladies Lysosomales (VML), Massy, France.
- Sophie Vibet: Centre d’Évaluation et de Traitement de la Douleur, CHRU Tours, Tours, France.
Contributions: Tardieu and Labarthe conceived the study; Blin and Labarthe analyzed data; all interpreted results and approved the manuscript.
Corresponding Author: François Labarthe (francois.labarthe@univ-tours.fr).
Ethics Declarations
Approved by University Hospital of Tours' committee (Ref. RNIPH21-AIE D MPS); informed consent obtained.
Conflict of Interest
Lacombe: fees from Sanofi-Genzyme (outside this work). Labarthe: consulting for AlfaSigma, Biomarin, Sanofi-Genzyme (outside this work). Others: none declared.
Publisher’s Note
Springer Nature maintains neutrality on jurisdictional claims.
Rights and Permissions
Licensed under Creative Commons Attribution 4.0 International License. For reprints: contact Springer Nature.
About This Article
Cite: Blin M, et al. Pain assessment and treatment in patients with mucopolysaccharidoses: a French multicentric pediatric study. Orphanet J Rare Dis 20, 581 (2025). https://doi.org/10.1186/s13023-025-04065-9
Received: April 15, 2024; Accepted: September 23, 2025; Published: November 12, 2025.
Keywords: Mucopolysaccharidoses, Pediatric pain, Pain assessment, Rare diseases, Multidimensional pain management.
